MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Addiction Biology' source. Tue, 07 Feb 2012 12:26:42 +0100 http://www.medworm.com/index.php?rid=5618550&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00418.x ABSTRACTThe cognitive repercussions of alcohol dependence are well documented. However, the literature remains somewhat ambiguous with respect to which distinct cognitive functions are more susceptible to impairment in alcoholism and to how duration of abstinence affects cognitive recovery. Some theories claim alcohol negatively affects specific cognitive functions, while others assert that deficits are more diffuse in nature. This is the first meta‐analysis to examine cognition in alcohol abuse/dependence and the duration of abstinence necessary to achieve cognitive recovery. A literature search yielded 62 studies that assessed cognitive dysfunction among alcoholics. Effect size estimates were calculated using the Comprehensive Meta‐Analysis V2, for the following 12 cognitive domains:... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5618550 Fri, 20 Jan 2012 05:00:00 +0100 5618550 http://www.medworm.com/index.php?rid=5618549&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00417.x ABSTRACTCue‐reactivity reflects enhanced motivational processing underlying continued substance use and relapse in substance use disorders. Substance use disorders are associated with greater cue‐reactivity in orbitofrontal cortex, anterior cingulate cortex, striatum, ventral tegmental area and amygdala. Here we examine whether this also holds for frequent cannabis users. Using functional magnetic resonance imaging (fMRI), neural responses to neutral and cannabis‐related cues were compared between frequent cannabis users (n = 31), sporadic cannabis users (n = 20) and cannabis‐naive controls (n = 21). In addition, fMRI findings were correlated with the level of cannabis use, problem severity and craving. In frequent users compared with sporadic users and controls, cannab... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5618549 Fri, 20 Jan 2012 05:00:00 +0100 5618549 http://www.medworm.com/index.php?rid=5618548&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00424.x ABSTRACTAlthough substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu‐CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu‐CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000‐fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu‐CocH (5 mg/kg) had a half‐life of 56.6 hours in squirrel monkeys. In these studies, pla... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5618548 Fri, 20 Jan 2012 05:00:00 +0100 5618548 http://www.medworm.com/index.php?rid=5618547&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00423.x ABSTRACTOne aspect of the addictive process that has not been thoroughly investigated is the consequence of the frustrated state occurring when the drug is not available. The present study aimed to validate a novel operant model of frustrated expected reward in mice. C57BL/6J mice were trained in operant conditioning maintained by chocolate‐flavoured pellets or cocaine. After the completion of high rates of responding on a progressive ratio schedule, the reward was unexpectedly withheld. The consequences of this frustrated behaviour on anxiety, aggressiveness, perseveration, extinction and reinstatement were investigated. Mice exposed to the frustrated event perseverated in the operant responses and showed increased aggressiveness in the resident—intruder test. These animals also showe... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5618547 Fri, 20 Jan 2012 05:00:00 +0100 5618547 http://www.medworm.com/index.php?rid=5606224&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00419.x ABSTRACTPre‐clinical studies suggest that the neurokinin‐1 (NK1) receptor may modulate the response to opioids, with NK1 inactivation leading to decreased opioid reinforcement, tolerance and withdrawal. Aprepitant is a selective NK1 antagonist currently marketed for clinical use as an anti‐emetic. This 6‐week in‐patient study used a randomized, double‐blind, double‐dummy, within‐subject, crossover design. Subjects (n = 8; 6 male/2 female) were healthy, adult volunteers who provided subjective and objective evidence of current prescription opioid abuse (without physical dependence) and underwent careful medical and psychiatric screening. Fifteen experimental conditions, consisting of one aprepitant dose (0, 40 and 200 mg, p.o. given as a 2‐hour pre‐treatment) in co... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5606224 Thu, 19 Jan 2012 05:00:00 +0100 5606224 http://www.medworm.com/index.php?rid=5606223&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00420.x ABSTRACTAcute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic–pituitary–adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol‐induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 fa... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5606223 Thu, 19 Jan 2012 05:00:00 +0100 5606223 http://www.medworm.com/index.php?rid=5606222&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00421.x ABSTRACTRepeated administration of 3,4‐methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non‐neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and attentional set‐shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5 days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in t... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5606222 Thu, 19 Jan 2012 05:00:00 +0100 5606222 http://www.medworm.com/index.php?rid=5606221&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00422.x This study examined the predictive relationships between initial level and growth of smoking and drinking in 311 early adolescents (13–15 years old) over a 4‐year period. In addition, the effects of the A118G polymorphism of the OPRM1 gene on the initial values and the development over time of alcohol use and smoking were assessed. Finally, as prevalence and heritability estimates for both alcohol‐ and smoking‐related behaviors differ between males and females, OPRM1 by sex interactions were tested. We found that high initial levels of early adolescent alcohol consumption were related to a stronger increase in smoking levels over time. In contrast, high initial levels of smoking were not related to growth of alcohol use. No main OPRM1 effects were found, but sex‐specificity of ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5606221 Thu, 19 Jan 2012 05:00:00 +0100 5606221 http://www.medworm.com/index.php?rid=5606220&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00425.x ABSTRACTMethamphetamine (METH) dependence is becoming a serious socioeconomic health problem worldwide. The enhancement of the cholinergic nervous system is expected to greatly alleviate drug dependence. We investigated the effect of galantamine on the reinstatement of cue‐induced METH‐seeking behavior using a self‐administration experiment. Treatment with galantamine (1 mg/kg, p.o.) 30 minutes before exposure to the cues suppressed the reinstatement of METH‐seeking behavior. However, galantamine did not affect the cue‐induced reinstatement of food‐seeking behavior or locomotor activity. These results suggest that galantamine may be a candidate drug for treating relapses of METH‐seeking behavior. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5606220 Thu, 19 Jan 2012 05:00:00 +0100 5606220 http://www.medworm.com/index.php?rid=5618546&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00430.x In this study, we examined whether naloxone‐induced cortisol and adrenocorticotropin (ACTH) responses in 15 healthy control and 20 recently detoxified alcohol‐dependent subjects correlated with delta opioid receptor (DOR) availability in 15 brain regions using the DOR‐selective ligand [11C] methyl‐naltrindole (MeNTL) and PET imaging. The day after the scan, cortisol responses to cumulative doses of naloxone were determined. Peak cortisol and ACTH levels and area under the cortisol and ACTH curve did not differ by group. There were negative relationships between cortisol area under curve to naloxone and [11C] MeNTL‐binding potential (BPND) in the ventral striatum, anterior cingulate, fusiform cortices, temporal cortex, putamen and a trend in the hypothalamus of healthy control sub... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5618546 Sun, 01 Jan 2012 05:00:00 +0100 5618546 http://www.medworm.com/index.php?rid=5606219&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00427.x ABSTRACTMarijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within�... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5606219 Sun, 01 Jan 2012 05:00:00 +0100 5606219 http://www.medworm.com/index.php?rid=5522232&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00397.x (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5522232 Wed, 21 Dec 2011 05:00:59 +0100 5522232 http://www.medworm.com/index.php?rid=5455509&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00408.x ABSTRACTThe use of addictive drugs can lead to long‐term neuroplastic changes in the brain, including behavioral sensitization, a phenomenon related to addiction. Environmental enrichment (EE) is a strategy used to study the effect of environment on the response to several manipulations, including treatment with addictive drugs. Brain‐derived neurotrophic factor (BDNF) has been associated with behaviors related to ethanol addiction. The aim of the present study was to evaluate the effects of EE on ethanol‐induced behavioral sensitization and BDNF expression. Mice were exposed to EE and then repeatedly treated with a low dose (1.8 g/kg) of ethanol. Another group of mice was first subjected to repeated ethanol treatment according to the behavioral sensitization protocol and then expo... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5455509 Tue, 29 Nov 2011 05:00:00 +0100 5455509 http://www.medworm.com/index.php?rid=5455508&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00412.x ABSTRACTMultiple lines of high alcohol‐preferring (HAP) mice were selectively bred for their intake of 10% ethanol (v/v) during 24‐hour daily access over a 4‐week period, with the highest drinking lines exhibiting intakes in excess of 20 g/kg/day. We observed circadian drinking patterns and resulting blood ethanol concentrations (BECs) in the HAP lines. We also compared the drinking rhythms and corresponding BECs of the highest drinking HAP lines to those of the C57BL/6J (B6) inbred strain. Adult male and female crossed HAP (cHAP), HAP replicate lines 1, 2, 3 and B6 mice had free‐choice access to 10% ethanol and water for 3 weeks prior to bi‐hourly assessments of intake throughout the dark portion of the light–dark cycle. All HAP lines reached and maintained a rate of alcohol... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5455508 Tue, 29 Nov 2011 05:00:00 +0100 5455508 http://www.medworm.com/index.php?rid=5455507&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00413.x ABSTRACTTo investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent–child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight‐wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachmen... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5455507 Tue, 29 Nov 2011 05:00:00 +0100 5455507 http://www.medworm.com/index.php?rid=5455506&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00414.x In this study, we examined regional cerebral blood flow (rCBF) during a saline infusion in two independent populations of abstinent cocaine‐ (and mostly nicotine‐) addicted (n = 33 and 26) and healthy control (n = 35 and 20) men and women. Isolated rCBF decreases (P < 0.001) were observed in the left caudolateral OFC, as well as left superior temporal cortex, in cocaine‐addicted subjects relative to controls in both cohorts and bilaterally in the combined cohort. An anatomically defined region of the caudolateral OFC showed similar findings and were evident in both male and female addicted subjects. The reliability of these findings across two cohorts reveals a functional disruption in the lateral OFC, a brain region implicated in the evaluation of behavior‐terminati... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5455506 Tue, 29 Nov 2011 05:00:00 +0100 5455506 http://www.medworm.com/index.php?rid=5455505&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00415.x ABSTRACTAlcohol activates orosensory circuits that project to motivationally relevant limbic forebrain areas that control appetite, feeding and drinking. To date, limited data exists regarding the contribution of chemosensory‐derived ethanol reinforcement to ethanol preference and consumption. Measures of taste reactivity to intra‐orally infused ethanol have not found differences in initial orofacial responses to alcohol between alcohol‐preferring (P) and alcohol‐non‐preferring (NP) genetically selected rat lines. Yet, in voluntary intake tests, P rats prefer highly concentrated ethanol upon initial exposure, suggesting an early sensory‐mediated attraction. Here, we directly compared self‐initiated chemosensory responding for alcohol and prototypic sweet, bitter and oral trig... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5455505 Tue, 29 Nov 2011 05:00:00 +0100 5455505 http://www.medworm.com/index.php?rid=5398654&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00407.x ABSTRACTChronic smoking in alcohol dependence is associated with abnormalities in brain morphology and metabolite levels in large lobar regions (e.g. frontal lobe). Here, we evaluated if these abnormalities are specifically apparent in several cortical and select subcortical components of the extended brain reward system (BRS), a network that is critically involved in the development and maintenance of all forms of addictive disorders. We studied 33 non‐smoking and 43 smoking alcohol‐dependent individuals (ALC) with 1 week of abstinence and 42 non‐smoking Controls. At 1.5 Tesla, we obtained regional measures of cortical thickness and N‐acetylaspartate (NAA; a surrogate marker of neuronal integrity) concentration in major components of the BRS as well as the corresponding measures t... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5398654 Wed, 09 Nov 2011 05:00:00 +0100 5398654 http://www.medworm.com/index.php?rid=5357242&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00224.x ABSTRACTThe effects of repeated, intermittent administration of a moderate dose of ethanol (3.4 g/kg/day × 6 days, intragastrically via gavages) on cognitive function were examined in male Wistar rats. No significant differences in weight gain between the ethanol‐ and water‐treated rats were found. Analysis of physical dependence revealed no signs of spontaneous withdrawal, whereas withdrawal signs exacerbated by Ro15‐4513, an inverse benzodiazepine agonist, were apparent 5 hours but not 24 hours after the cessation of ethanol treatment. Spatial learning and memory, as assessed in the Barnes maze, were impaired 3–6 days following the treatment but recovered by the 11th–14th days. Reversal learning, however, was impaired throughout the 2‐week observation period. Thus, bou... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5357242 Wed, 26 Oct 2011 04:00:00 +0100 5357242 http://www.medworm.com/index.php?rid=5357241&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00391.x This study investigated the correlation between seven markers throughout hDAT and its mRNA levels in postmortem ventral midbrain tissues from 18 cocaine abusers and 18 strictly matched drug‐free controls in the African‐American population. Here, we show that one major haplotype with the same frequency in cocaine abusers versus drug‐free controls displays a 37.1% reduction of expression levels in cocaine abusers compared with matched controls (P = 0.0057). The most studied genetic marker, variable number tandem repeats (VNTR) located in Exon 15 (3′VNTR), is not correlated with hDAT mRNA levels. A 5′ upstream VNTR (rs70957367) has repeat numbers that are positively correlated with expression levels in controls (r2 = 0.9536, P = 0.0235), but this positive correlation dis... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5357241 Wed, 26 Oct 2011 04:00:00 +0100 5357241 http://www.medworm.com/index.php?rid=5345261&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00392.x ABSTRACTGhrelin (GHR) is an orexigenic gut peptide that interacts with brain ghrelin receptors (GHR‐Rs) to promote food intake. Recent research suggests that GHR acts as a modulator of motivated behavior, suggesting a direct influence of GHR on brain reinforcement circuits. In the present studies, we investigated the role of GHR and GHR‐Rs in brain reinforcement function. Pharmacological magnetic resonance imaging was used to spatially resolve the functional activation produced by systemic administration of an orexigenic GHR dose. The imaging data revealed a focal activation of a network of subcortical structures that comprise brain reinforcement circuits—ventral tegmental area, lateral hypothalamus and nucleus accumbens. We next analyzed whether brain reinforcement circuits require ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5345261 Fri, 21 Oct 2011 04:00:00 +0100 5345261 http://www.medworm.com/index.php?rid=5345260&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00394.x ABSTRACTHuman studies indicate that high impulsivity, novelty seeking and anxiety predispose individuals to alcohol abuse. Unclear, however, is whether the same phenotypes can be observed in laboratory animals prone to uncontrolled alcohol drinking. To characterize a novelty‐seeking trait, anxiety, impulsivity, compulsivity and the motivation for natural rewards in mice, numerous tests were performed in the automated IntelliCage learning system. The same mice then had extended access to alcohol for 70 days, followed by the evaluation of addiction‐like behaviors, including (1) the motivation for alcohol in a progressive‐ratio schedule of reinforcement; (2) persistent and compulsive alcohol seeking and taking during signaled ‘no alcohol’ periods and (3) when subjected to punishment... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5345260 Fri, 21 Oct 2011 04:00:00 +0100 5345260 http://www.medworm.com/index.php?rid=5333307&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00395.x ABSTRACTAlcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome‐wide association study (GWAS). The sample comprised 1333 male in‐patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single‐marker tests and a polygenic score‐based analysis to assess the combined contribution of multiple markers with small effects were performed. The sing... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5333307 Tue, 18 Oct 2011 04:00:00 +0100 5333307 http://www.medworm.com/index.php?rid=5312510&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00381.x ABSTRACTStudies have shown that various brain structure abnormalities are associated with chronic alcohol abuse and impulsive aggression. However, few imaging studies have focused on violent individuals with a diagnosis of alcohol dependence. The present study used volumetric magnetic resonance imaging (MRI) to compare the volumes of different structural components of prefrontal cortex and six subcortical structures in perpetrators of intimate partner violence with alcohol dependence (IPV‐ADs), non‐violent alcohol‐dependent patients (non‐violent ADs) and healthy controls (HCs). Caucasian men (n = 54), ages 24–55, who had participated in National Institutes of Alcohol Abuse and Alcoholism treatment programs, were grouped together as IPV‐ADs (n = 27), non‐violent ADs (n... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312510 Thu, 13 Oct 2011 04:00:00 +0100 5312510 http://www.medworm.com/index.php?rid=5312509&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00382.x ABSTRACTMany adolescents often take ethanol (EtOH) in combination with 3,4‐methylenedioxymethylamphetamine (MDMA). In the present work, we used a mouse model to study the effect of repeated pre‐exposure during adolescence to EtOH (2 g/kg), MDMA (10 or 20 mg/kg) or EtOH + MDMA on the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm. Pre‐exposure to EtOH, MDMA or both increased the rewarding effects of a low dose of MDMA (1.25 mg/kg). These pre‐treatments did not affect the acquisition of the CPP induced by 5 mg/kg of MDMA. However, the CPP was more persistent in mice pre‐exposed to both doses of MDMA or to EtOH + MDMA20. After extinction of the CPP induced by 5 mg/kg of MDMA, reinstatement was observed in all groups wit... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312509 Thu, 13 Oct 2011 04:00:00 +0100 5312509 http://www.medworm.com/index.php?rid=5312508&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00383.x This study suggests that alcohol may increase risk‐taking behavior by both activating brain regions involved in reward when a decision is made, and dampening the response to negative and positive feedback. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312508 Thu, 13 Oct 2011 04:00:00 +0100 5312508 http://www.medworm.com/index.php?rid=5312507&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00384.x ABSTRACTMephedrone (4‐methylmethcathinone) is a novel recreational drug that has rapidly increased in popularity in recent years. Users report mephedrone as having the stimulant‐like qualities of methamphetamine and cocaine, combined with the prosocial, entactogenic effects of 3,4‐methylenedioxymethamphetamine (MDMA). Anecdotal and case study reports indicate that mephedrone may have the potential to engender compulsive patterns of use as well as toxicity in overdose. However, there have been almost no neuropharmacological investigations of the drug up to this point. Here we examined the effects of two different mephedrone doses [15 and 30 mg/kg, intraperitoneal (IP)] relative to the well‐known stimulant methamphetamine (2 mg/kg IP) in adolescent rats. Rats were injected, asses... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312507 Thu, 13 Oct 2011 04:00:00 +0100 5312507 http://www.medworm.com/index.php?rid=5312506&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00385.x ABSTRACTIncreased drug availability can precipitate a rapid escalation of drug consumption in both vulnerable humans and laboratory animals. Drug intake escalation is observed across a broad spectrum of drugs of abuse, including stimulants, opiates, ethanol and phencyclidine. Whether and to what extent the processes underlying escalated levels of drug intake vary across different substances is poorly understood. The present study sought to address this question in rats self‐administering both cocaine and heroin—two addictive drugs with both common and different neurobiological effects. In experiment 1, we determined how cocaine intake is initially related to heroin intake in non‐escalated rats with a limited access to both drugs. In experiment 2, two groups of rats were initially all... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312506 Thu, 13 Oct 2011 04:00:00 +0100 5312506 http://www.medworm.com/index.php?rid=5312505&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00387.x ABSTRACTThe present study evaluated the involvement of the dorsal hippocampal cannabinoid CB1 receptors in the combined effect of ethanol and nicotine on passive avoidance learning in adult male mice. The results indicated that pre‐training administration of ethanol (1 g/kg, i.p.) impaired memory retrieval. Pre‐test administration of ethanol (0.5 and 1 g/kg, i.p.) or nicotine (0.5 and 0.7 mg/kg, s.c.) significantly reversed ethanol‐induced amnesia, suggesting a functional interaction between ethanol and nicotine. Pre‐test microinjection of a selective CB1 receptor agonist, ACPA (3 and 5 ng/mouse), plus an ineffective dose of ethanol (0.25 g/kg) or nicotine (0.3 mg/kg) improved memory retrieval, while ACPA by itself could not reverse ethanol‐induced amnesia. Pre‐test... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312505 Thu, 13 Oct 2011 04:00:00 +0100 5312505 http://www.medworm.com/index.php?rid=5312504&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00389.x ABSTRACTEvidence suggests that acute exposure to (+/‐)3,4‐methylenedioxymethamphetamine (MDMA) produces qualitatively similar effects on recognition task performance as other stimulant‐type drugs. The current study examined whether there was a similar neurochemical basis to these memory effects by examining the effects of a D1 receptor antagonist (SCH23390) and D2 antagonist (eticlopride) on MDMA‐ or cocaine‐induced impairments in delayed matching‐to‐sample performance in rats. At low doses it was shown that eticlopride was ineffective in antagonizing either MDMA or cocaine's effects, and at higher doses exacerbated their effects. In contrast, the D1 receptor antagonist SCH23390 was only able to significantly attenuate the disruption caused by MDMA, but not cocaine's effects.... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312504 Thu, 13 Oct 2011 04:00:00 +0100 5312504 http://www.medworm.com/index.php?rid=5312503&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00390.x ABSTRACTHeroin dependence is a complex mental disorder resulting from interactions between genetic and environmental factors. Identifying the susceptibility genes of heroin dependence is the basis for understanding the pathogenesis of heroin dependence. Using a total gene expression microarray, we detected 924 differentially expressed gene transcripts in lymphoblastoid cell lines (LCLs) between 19 male heroin‐dependent individuals and 20 male control subjects, including 279 upregulated and 645 downregulated gene transcripts in heroin‐dependent individuals. We verified the reduced expression of the neuron‐specific enolase gene (ENO2) in heroin‐dependent individuals using real‐time quantitative polymerase chain reaction and Western blot analysis. We further compared the allele and ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312503 Thu, 13 Oct 2011 04:00:00 +0100 5312503 http://www.medworm.com/index.php?rid=5312502&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00393.x In this study, we investigate the relationship of genome‐wide CNVs with brain function elicited by an alcohol cue in 300 participants with alcohol use disorders. First, we extracted refined neurobiological phenotypes, the brain responses to an alcohol cue versus a juice cue in the precuneus, thalamus and anterior cingulate cortex (ACC). Then, we correlated the CNVs with incidence frequency > 1% to the neurobiological phenotypes. One CNV region at 22q13.1 was identified to be associated with alcohol dependence severity and the brain response to alcohol cues. Specifically, the 22k base‐pair homozygous deletion at 22q13.1 affects genes APOBEC3a and APOBEC3b. Carriers of this homozygous deletion show a significantly higher score in the alcohol dependence severity (P < 0.05) and... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312502 Thu, 13 Oct 2011 04:00:00 +0100 5312502 http://www.medworm.com/index.php?rid=5283280&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00371.x The objective of this study was to determine the relationship between a number of clinical variables—severity of alcoholism, family history of alcoholism (FHA+), personality traits related to the sensitivity to reward—and the startle reflex response when subjects with alcohol dependence were viewing alcohol‐related cues. After detoxification, 98 participants completed self‐report instruments and had eye blink electromyograms measured to acoustic startle probes [100‐millisecond burst of white noise at 95 dB(A)] while viewing alcohol‐related pictures, and standardised appetitive, aversive and neutral control scenes. Ninety‐eight healthy controls were also assessed with the same instruments. There were significant differences on alcohol‐startle magnitude between patients and... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283280 Tue, 04 Oct 2011 04:00:00 +0100 5283280 http://www.medworm.com/index.php?rid=5283279&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00372.x In conclusion, using ERPs, a direct measure of brain activity, we found that smokers with blunted brain responses to intrinsically pleasant stimuli had lower rates of long‐term smoking abstinence. This response offers a new biomarker for identifying smokers at higher risk of relapse and for testing the efficacy of new interventions aimed at normalizing brain reward systems' responses to intrinsically pleasant stimuli. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283279 Tue, 04 Oct 2011 04:00:00 +0100 5283279 http://www.medworm.com/index.php?rid=5283277&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00374.x We report that injections of the CRF receptor antagonist d‐Phe CRF into the median raphe nucleus (MRN) attenuated yohimbine‐induced reinstatement of alcohol seeking but had no effect on yohimbine‐induced increases in alcohol intake during ongoing self‐administration. Results indicate an important role of MRN CRF receptors in yohimbine‐induced reinstatement of alcohol seeking but not yohimbine‐induced increases in alcohol intake. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283277 Tue, 04 Oct 2011 04:00:00 +0100 5283277 http://www.medworm.com/index.php?rid=5283276&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00373.x ABSTRACTAgmatine, an endogenous ligand for imidazoline receptor, has been shown to prevent opioid dependence, but not much is known about the mechanisms of the effect of agmatine. In the present study, we investigated the function of I1 imidazoline receptor and its candidate protein imidazoline receptor antisera‐selected (IRAS)/Nischarin in morphine dependence as well as in the effect of agmatine inhibiting morphine dependence by pharmacological and molecular approaches. Results showed that inhibition of IRAS or Nischarin did not change the development of morphine dependence in vitro and in vivo under the basal condition. Agmatine could reduce the cyclic 3′, 5′ adenosine monophosphate (cAMP) overshoot at the concentration of 0.01–10 µM in the primary cultured rat hippocampal neu... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283276 Tue, 04 Oct 2011 04:00:00 +0100 5283276 http://www.medworm.com/index.php?rid=5283275&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00376.x ABSTRACTTobacco and alcohol dependence are characterized by continued use despite deleterious health, social and occupational consequences, implying that addicted individuals pay a high price for their use. In behavioral economic terms, such persistent consumption despite increased costs can be conceptualized as inelastic demand. Recent animal studies demonstrated that high‐impulsive individuals are more willing to work for nicotine or cocaine infusions than their low‐impulsive counterparts, indicating that this trait might be causally related to inelastic drug demand. By employing progressive ratio schedules of reinforcement combined with a behavioral economics approach of analysis, we determined whether trait impulsivity is associated with an insensitivity of nicotine or alcohol cons... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283275 Tue, 04 Oct 2011 04:00:00 +0100 5283275 http://www.medworm.com/index.php?rid=5283274&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00375.x ABSTRACTStress contributes to the development of ethanol dependence and is also a consequence of dependence. However, the complexity of physiological interactions between activation of the hypothalamic–pituitary–adrenal (HPA) axis and ethanol itself is not well delineated. Emerging evidence derived from examination of corticotropin‐releasing factor systems and glucocorticoid receptor systems in ethanol dependence suggests a role for pharmacological manipulation of the HPA axis in attenuating ethanol intake, though it is not clear how activation of the HPA axis may promote ethanol dependence or contribute to the neuroadaptative changes that accompany the development of dependence and the severity of ethanol withdrawal. This review examines the role that glucocorticoids, in particular,... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283274 Tue, 04 Oct 2011 04:00:00 +0100 5283274 http://www.medworm.com/index.php?rid=5283273&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00377.x ABSTRACTThere is converging evidence suggesting a particular susceptibility to the addictive properties of nicotine among adolescents. The aim of the current study was to prospectively ascertain the relationship between age at first cigarette and initial smoking experiences, and to examine the combined effects of these characteristics of adolescent smoking behavior on adult smoking. It was hypothesized that the association between earlier age at first cigarette and later development of nicotine dependence may, at least in part, be attributable to differences in experiencing pleasurable early smoking sensations. Data were drawn from the participants of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. Structured interviews at age 15, 19... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283273 Tue, 04 Oct 2011 04:00:00 +0100 5283273 http://www.medworm.com/index.php?rid=5283272&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00379.x ABSTRACTDrug addiction is thought to result from an intractable and aberrant learning and memory in response to drug‐related stimulation, and cholinergic neurotransmission plays an important role in this process. Phosphatidylethanolamine‐binding protein (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP), an 11 amino acid peptide that enhances the production of choline acetyltransferase (ChAT) and assists in the development of cholinergic projections from the medial septal nuclei to the hippocampus. However, whether PEBP is involved in drug addiction remains unclear. In the present study, PEBP expression in the hippocampus, as detected by proteomics analysis, was found to be dramatically up‐regulated after rats received chronic morphine treatment. W... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283272 Tue, 04 Oct 2011 04:00:00 +0100 5283272 http://www.medworm.com/index.php?rid=5283270&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00378.x ABSTRACTThe purpose of this study was to examine the role of the prodynorphin gene in alcohol sensitivity, preference and vulnerability to alcohol consumption. Handling‐induced convulsion (HIC) associated to alcohol, alcohol‐induced loss of righting reflex (LORR), hypothermic effects in response to acute ethanol challenge, blood ethanol levels (BELs), conditioned place preference, voluntary ethanol consumption and preference, tyrosine hydroxylase (TH), dopamine transporter (DAT) and proenkephalin (PENK) gene expression, and µ‐, δ‐ and κ‐opioid agonist‐stimulated [S35]‐ guanosine 5′‐triphosphate‐binding autoradiography were studied in prodynorphin knockout (PDYN KO) and wild‐type (WT) mice. There were no differences in HIC, LORR or the decrease in body temperature i... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283270 Tue, 04 Oct 2011 04:00:00 +0100 5283270 http://www.medworm.com/index.php?rid=5283281&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00355.x ABSTRACTPositron emission tomography (PET) shows reduced binding of the dopamine D2/3 antagonist [11C]raclopride in striatum of withdrawn psychostimulant abusers, but not consistently in patients with alcohol dependence (AD). We make first use of the high affinity ligand [18F]fallypride to obtain serial measures of D2/3 receptor availability in striatal and extrastriatal regions of AD patients undergoing detoxification. Seventeen patients (mean age 44 ± 5y) with AD and 14 age‐matched healthy volunteers participated. Each patient underwent [18F]fallypride PET upon hospital admission, and again 1–2 weeks later; two patients achieving abstinence, and two with substantial harm reduction had additional PET follow‐up at 1 year. Dynamic 180‐minute PET recordings were used for vol... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283281 Mon, 03 Oct 2011 04:00:00 +0100 5283281 http://www.medworm.com/index.php?rid=5455504&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00416.x This study supports preliminary findings that humans, like animals, develop a preference for a place associated with d‐amphetamine that is related to its subjective effects. These findings also suggest that experiencing d‐amphetamine in a consistent environment produces context‐dependent changes in its subjective effects, including an enhanced rewarding efficacy and abuse potential. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5455504 Sat, 01 Oct 2011 04:00:00 +0100 5455504 http://www.medworm.com/index.php?rid=5420227&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00410.x In this study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of smoking abstinence on emotional information processing. Smokers (n = 17) and non‐smokers (n = 18) underwent fMRI while performing an emotional distractor oddball task in which rare targets were presented following negative and neutral task‐irrelevant distractors. Smokers completed two sessions: once following 24‐hour abstinence and once while satiated. The abstinent versus satiated states were compared by evaluating responses to distractor images and to targets following each distractor valence within frontal executive and limbic brain regions. Regression analyses were done to investigate whether self‐reported negative affect influences brain response to images and targets. Ex... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5420227 Sat, 01 Oct 2011 04:00:00 +0100 5420227 http://www.medworm.com/index.php?rid=5398653&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00409.x ABSTRACTEpigenetic processes have been implicated in neuronal plasticity following repeated cocaine application. Here we measured DNA methylation at promoter CpG sites of the dopamine transporter (DAT1) and serotonin transporter (SERT) and neurokinin3‐receptor (NK3‐R)‐receptor (TACR3) coding genes in marmoset monkeys after repeated cocaine injections in a conditioned place preference paradigm. We found a decrease in DNA methylation at a specific CpG site in TACR3, but not DAT1 or SERT. Thus, TACR3 is a locus for DNA methylation changes in response to repeated cocaine administration and its establishment as a reinforcer, in support of other evidence implicating the NK3‐R in reinforcement‐ and addiction‐related processes. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5398653 Sat, 01 Oct 2011 04:00:00 +0100 5398653 http://www.medworm.com/index.php?rid=5380324&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00411.x In this study, the association between brain‐derived neurotrophic factor (BDNF) and pathological gambling was investigated. We measured BDNF serum levels in (1) video players (n = 10); (2) card players (n = 9); (3) mixed players (n = 21; both video and card players) and (4) age‐matched controls (n = 18). Mixed players had increased BDNF serum levels as compared to controls and higher South Oaks Gambling Screen score as compared to card or video players. Thus, the data demonstrate that patients affected by severe pathological gambling show enhanced BDNF serum levels. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5380324 Sat, 01 Oct 2011 04:00:00 +0100 5380324 http://www.medworm.com/index.php?rid=5357240&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00405.x This study aimed to evaluate brain correlates of cue‐induced craving to play online games in subjects with Internet gaming addiction (IGA), subjects in remission from IGA and controls. The craving response was assessed by event‐related design of functional magnetic resonance images (fMRIs). Fifteen subjects with IGA, 15 in remission from IGA and 15 controls were recruited in this study. The subjects were arranged to view the gaming screenshots and neutral images under investigation of fMRIs. The results showed that bilateral dorsolateral prefrontal cortex (DLPFC), precuneus, left parahippocampus, posterior cingulate and right anterior cingulate were activated in response to gaming cues in the IGA group and their activation was stronger in the IGA group than those in the control group. ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5357240 Sat, 01 Oct 2011 04:00:00 +0100 5357240 http://www.medworm.com/index.php?rid=5345259&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00406.x This study examined the actions of pregabalin and topiramate on behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice.Tolerance was induced in mice by administration of CP‐55,940 (0.5 mg/kg/12 hours; i.p.; 7 days). Behavioural assessment of spontaneous cannabinoid withdrawal was performed by measuring motor activity, somatic signs and anxiety‐like behaviour on days 1 and 3 after cessation of treatment with CP‐55,940. On days 1–3 of cannabinoid withdrawal, mice received pregabalin (40 mg/kg/12 hours; p.o.) or topiramate (50 mg/kg/12 hours; p.o.) and their actions on signs of withdrawal and anxiety‐like behaviour were evaluated.The administration of CP‐55,940 decreased rectal temperature and motor activity on day 1. On day 1 af... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5345259 Sat, 01 Oct 2011 04:00:00 +0100 5345259 http://www.medworm.com/index.php?rid=5333306&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00404.x ABSTRACTThe Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ‐amino butyric acid (GABA) transmission are significantly altered after cocaine‐induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate and GABA responsiveness to cocaine‐induced reinstatement remains unknown. To investigate this, we measured by in vivo microdialysis extracellular glutamate and GABA levels in the core division of the nucleus accumbens after extinction of cocaine self‐administration and during cocaine‐induced reinstatement (7.5 mg/kg, i.p.) in these two strains of rats. No strain differences were evident in cocaine self‐administration or ex... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5333306 Sat, 01 Oct 2011 04:00:00 +0100 5333306 http://www.medworm.com/index.php?rid=5312501&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00396.x ABSTRACTFood deprivation (FD) or restriction augments the locomotor activating and reinforcing effects of drugs of abuse. It has been proposed that these effects might be mediated by FD‐induced increase in plasma levels of ghrelin, a 28‐amino acid orexigenic peptide demonstrated to functionally interact with the mesolimbic dopaminergic system. However, a role for ghrelin has been demonstrated only with psychostimulant drugs and alcohol associated behaviors. We therefore examined the role of ghrelin in ongoing heroin self‐administration and FD‐induced reinstatement of extinguished heroin seeking. As expected, infusions of ghrelin [0.0, 1.5 and 3.0 µg/rat, intracerebroventricular (i.c.v.)] produced increases in breakpoints on a progressive ratio schedule of heroin reinforcement. I... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5312501 Sat, 01 Oct 2011 04:00:00 +0100 5312501 http://www.medworm.com/index.php?rid=5283269&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00380.x ABSTRACTEvidence for the assumption that cannabis use is associated with depression and depressive symptoms is inconsistent and mostly weak. It is likely that the mixed results are due to the fact that prior studies ignored the moderating effects of an individual's genetic vulnerability. The present study takes a first step in scrutinizing the relationship between cannabis use and depressive symptoms by taking a developmental molecular–genetic perspective. Specifically, we concentrated on changes in cannabis use and depressive symptoms over time in a simultaneous manner and differences herein for individuals with and without the short allele of the 5‐hydroxytryptamine (serotonin) transporter gene‐linked polymorphic region (5‐HTTLPR) genotype. Data were from 310 adolescents over a p... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5283269 Sat, 01 Oct 2011 04:00:00 +0100 5283269 http://www.medworm.com/index.php?rid=5271517&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00369.x This study shows that chronic treatment of rats with rimonabant (1.0 and 3.0 mg/kg/day) dose‐dependently increased DRD2 availability in the dorsal striatum (14 and 23%) compared with vehicle. High‐dose rimonabant also increased DRD2 availability in the ventral striatum (12%) and reduced weight gain. Thus, up‐regulation of striatal DRD2 by chronic rimonabant administration may be an underlying mechanism of action and confirms the interactions of the endocannabinoid and dopaminergic systems. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271517 Sat, 01 Oct 2011 04:00:00 +0100 5271517 http://www.medworm.com/index.php?rid=5271518&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00364.x ABSTRACTInhalants, frequently abused during adolescence, are neurotoxic to white matter. We investigated the impact of inhalant misuse on the morphology of the corpus callosum (CC), the largest white matter bundle in the brain, in an adolescent sample of inhalant users [n = 14; mean age = 17.3; standard deviation (SD) = 1.7], cannabis users (n = 11; mean age = 19.7; SD = 1.7) and community controls (n = 9; mean age = 19.5; SD = 2.6). We identified significant morphological differences in the CC among inhalant users compared with community controls. There were no morphological differences between inhalant and cannabis users. Our findings may represent the early stages of neurobiological damage associated with chronic inhalant misuse. (Source: Addiction Bi... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271518 Thu, 29 Sep 2011 04:00:00 +0100 5271518 http://www.medworm.com/index.php?rid=5271525&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00360.x We examined the effects of galanin in CeA slices from wild‐type and knockout (KO) mice deficient of GalR2 and both GalR1 and GalR2 receptors. Galanin had dual effects on gamma‐aminobutyric acid (GABA)‐ergic transmission, decreasing the amplitudes of pharmacologically isolated GABAergic inhibitory postsynaptic potentials (IPSPs) in over half of CeA neurons but augmenting IPSPs in the others. The increase in IPSP size was absent after superfusion of the GalR3 antagonist SNAP 37889, whereas the IPSP depression was absent in CeA neurons of GalR1 × GalR2 double KO and GalR2 KO mice. Paired‐pulse facilitation studies showed weak or infrequent effects of galanin on GABA release. Thus, galanin may act postsynaptically through GalR3 to augment GABAergic transmission in some CeA neurons... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271525 Wed, 28 Sep 2011 04:00:00 +0100 5271525 http://www.medworm.com/index.php?rid=5271524&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00363.x ABSTRACTThree experiments used the intragastric alcohol consumption (IGAC) procedure to examine the effects of variations in passive ethanol exposure on withdrawal and voluntary ethanol intake in two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2). Experimental treatments were selected to induce quantitative differences in ethanol dependence and withdrawal severity by: (1) varying the periodicity of passive ethanol exposure (three, six or nine infusions/day); (2) varying the dose per infusion (low, medium or high); and (3) varying the duration of passive exposure (3, 5 or 10 days). All experiments included control groups passively exposed to water. B6 mice generally self‐infused more ethanol than D2 mice, but passive ethanol exposure increased IGAC in both strains, with D2 mice showi... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271524 Wed, 28 Sep 2011 04:00:00 +0100 5271524 http://www.medworm.com/index.php?rid=5271523&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00365.x This study demonstrates that, regardless the drug, a specific set of transcriptional regulations develops in the abstinent brain, which possibly contributes to the negative affect characterizing protracted abstinence. This transcriptional signature may represent a hallmark of drug abstinence and a unitary adaptive molecular mechanism in substance abuse disorders. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271523 Wed, 28 Sep 2011 04:00:00 +0100 5271523 http://www.medworm.com/index.php?rid=5271522&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00366.x ABSTRACTThe endogenous opioid system (EOS) plays a critical role in addictive processes. Molecular dysregulations in this system may be specific for different stages of addiction cycle and neurocircuitries involved and therefore may differentially contribute to the initiation and maintenance of addiction. Here we evaluated whether the EOS is altered in brain areas involved in cognitive control of addiction including the dorsolateral prefrontal cortex (dl‐PFC), orbitofrontal cortex (OFC) and hippocampus in human alcohol‐dependent subjects. Levels of EOS mRNAs were measured by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), and levels of dynorphins by radioimmunoassay (RIA) in post‐mortem specimens obtained from 14 alcoholics and 14 controls. Prodynorphin mR... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271522 Wed, 28 Sep 2011 04:00:00 +0100 5271522 http://www.medworm.com/index.php?rid=5271521&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00367.x ABSTRACTExtracellular glycine modulates accumbal dopamine levels as well as ethanol‐induced dopamine overflow. Glycine availability is also crucial for regulating alcohol consumption and the glycine transporter 1 (GlyT‐1) inhibitor Org25935 robustly decreases alcohol intake in rats. To explore whether the alcohol‐intake reducing effect of Org25935 is substance bound, we examined the effect of a different selective GlyT‐1 inhibitor, Org24598, on ethanol consumption in rats and compared the effect with that of acamprosate, a drug currently in clinical use. We studied the effects of daily Org24598 and acamprosate injections on male Wistar rats with ∼60% ethanol preference in a limited access two bottle free‐choice model for 12 days, followed by alcohol deprivation for 14 days befo... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271521 Wed, 28 Sep 2011 04:00:00 +0100 5271521 http://www.medworm.com/index.php?rid=5271520&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00368.x This study tested the hypothesis that rats choose to refrain from cocaine self‐administration because cocaine would be conflictual, having both rewarding and anxiogenic properties. Contrary to this hypothesis, however, we report here that diazepam—a broad‐spectrum benzodiazepine anxiolytic—did not decrease, but instead, further increased cocaine abstinence. Interestingly, although diazepam decreased locomotion, rats adapted to this effect by spending more time near the lever associated with the preferred reward, a behavior that minimized the need for locomotion at the moment of choice. When responding for cocaine or saccharin was analyzed separately, we found that diazepam decreased responding for cocaine without affecting responding for saccharin. Finally, the abstinence‐promoti... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271520 Wed, 28 Sep 2011 04:00:00 +0100 5271520 http://www.medworm.com/index.php?rid=5271519&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00370.x In this study, tissue levels of 5HT in the frontal cortex, striatum and hippocampus were measured following different levels of self‐administered MDMA. For both groups, responding was initially reinforced by an infusion of 1.0 mg/kg/infusion MDMA. The dose was reduced to 0.5 mg/kg/infusion once 90 infusions had been self‐administered. For the two groups, testing continued until either a total of 165 or 315 mg/kg had been self‐administered. Assays were conducted either 2 or 10 weeks following the last self‐administration session. The lower dose exposure regimen failed to significantly decrease 5HT levels in any brain region. The higher dose exposure, however, decreased 5HT levels by 30–35% in all three brain regions 2 weeks, but not 10 weeks, following self‐administration.... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5271519 Wed, 28 Sep 2011 04:00:00 +0100 5271519 http://www.medworm.com/index.php?rid=5235854&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00388.x We examined publication trends in different subject categories of journals including general and multi‐disciplinary science, neuroscience, pharmacology, psychiatry and, as a final and most important category, substance abuse. In this first report, we provide a brief comprehensive overview on what has been published in terms of addiction in the general and multi‐disciplinary science category versus Addiction Biology within the past decade. We reviewed the literature within three time windows 1999/2000, 2004/2005 and 2009/2010 and selected the number of publications (1) according to the country/region where the original study was conducted; (2) according to the drug classes; (3) according to animal versus human studies; (4) and in terms of methodological trends such as genetic associatio... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5235854 Wed, 21 Sep 2011 00:56:58 +0100 5235854 http://www.medworm.com/index.php?rid=5235853&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00386.x ABSTRACTResearch on the biology of addiction has advanced significantly over the last 50 years expanding our understanding of the brain mechanisms underlying reward, reinforcement and craving. Novel experimental approaches and techniques have provided an ever increasing armory of tools to dissect behavioral processes, neural networks and molecular mechanisms. The ultimate goal is to reintegrate this knowledge into a coherent, mechanistic framework of addiction to help identify new treatment. This can be greatly facilitated by using tools that allow, with great spatial and temporal specificity, to link molecular changes with altered activation of neural circuits and behavior. Such specificity can now be achieved by using optogenetic tools. Our review describes the general principles of opto... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5235853 Wed, 21 Sep 2011 00:56:57 +0100 5235853 http://www.medworm.com/index.php?rid=5095941&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00348.x ABSTRACTAlcohol use is highly heritable and has been associated with many gene variants, including those related to dopamine (DA). However, single gene association studies have shown inconsistent and small effects. Using a system‐level approach, the current study aimed to estimate the overall effect of genetic variations in the DA system on alcohol use among male drinkers. One hundred seventy‐six male college students who reported to have ever drunk alcohol were enrolled. Alcohol use was measured using the Alcohol Use Disorders Identification Test. Ninety‐eight representative polymorphisms in all major DA neurotransmitter genes were genotyped. Using analysis of variance, we identified six single‐nucleotide polymorphisms (SNP)s that made statistically significant contributions to al... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095941 Wed, 03 Aug 2011 23:00:00 +0100 5095941 http://www.medworm.com/index.php?rid=5095940&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00353.x ABSTRACTCocaine abuse leads to adaptations in brain reward circuits, where dopaminergic neurotransmission is a fundamental component. We hypothesized that chronic cocaine self‐administration could influence dopamine D1 and D2 receptor activation of extracellular signal‐regulated protein kinase 1 and 2 (ERK1/2) and cyclic adenosine monophosphate response element‐binding protein (CREB) phosphorylation. Male Sprague Dawley rats were exposed to cocaine self‐administration for 6–11 weeks. Brains from sham controls and cocaine rats were extracted 1 day after the last session, and slices obtained from the striatum and nucleus accumbens (NAc) were incubated in vitro with or without the D1R agonist SKF38393 or the D2R agonist quinpirole. We found that cocaine self‐administration led to ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095940 Wed, 03 Aug 2011 23:00:00 +0100 5095940 http://www.medworm.com/index.php?rid=5095939&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00354.x ABSTRACTIn the present study, we investigated the possible development of tolerance to the antihyperalgesic effect of µ‐opioid receptor (MOR) agonists under a neuropathic pain‐like state. Repeated treatment with fentanyl, but not morphine or oxycodone, produced a rapid development of tolerance to its antihyperalgesic effect in mice with sciatic nerve ligation. Like the behavioral study, G‐protein activation induced by fentanyl was significantly reduced in membranes obtained from the spinal cord of nerve‐ligated mice with in vivo repeated injection of fentanyl. In β‐endorphin‐knockout mice with nerve ligation, developed tolerance to the antihyperalgesic effect of fentanyl was abolished, and reduced G‐protein activation by fentanyl after nerve ligation with fentanyl was rever... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095939 Wed, 03 Aug 2011 23:00:00 +0100 5095939 http://www.medworm.com/index.php?rid=5095938&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00356.x ABSTRACTThe dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long‐term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extrastriatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age‐matched subjects were compared: 11 healthy non‐smoker subjects, 14 tobacco‐dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [11... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095938 Wed, 03 Aug 2011 23:00:00 +0100 5095938 http://www.medworm.com/index.php?rid=5095937&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00357.x ABSTRACTNeuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various brain regions. The present study investigated brain region‐specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High‐density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi‐ar... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095937 Wed, 03 Aug 2011 23:00:00 +0100 5095937 http://www.medworm.com/index.php?rid=5095936&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00358.x ABSTRACTEnvironmental enrichment (EE) during a period of forced abstinence attenuates incentive motivational effects of cocaine‐paired stimuli. Here we examined whether EE during forced abstinence from cocaine self‐administration would prevent time‐dependent increases in cue‐elicited cocaine‐seeking behavior (i.e. the incubation effect). Rats were trained to self‐administer cocaine, which was paired with light/tone cues, for 15 days while living in isolated conditions (IC). Controls received yoked saline infusions. Subsequently, rats were assigned to live in either continued IC or EE for either 1 or 21 days of forced abstinence prior to a test for cocaine‐seeking behavior. During testing, responding resulted only in presentation of the light/tone cues. Contrary to our pre... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095936 Wed, 03 Aug 2011 23:00:00 +0100 5095936 http://www.medworm.com/index.php?rid=5095935&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00359.x ABSTRACTRecent studies have documented declined global cognitive function and abnormal task‐related brain activation in chronic cigarette smokers. However, the effects of long‐term heavy smoking on task‐independent baseline brain activity are still unknown. Here, we used a regional homogeneity (ReHo) method combined with functional magnetic resonance imaging (fMRI) to investigate spontaneous neural activity in the resting state in heavy smokers. Compared with controls, heavy smokers exhibited decreased ReHo in prefrontal regions, as well as increased ReHo in insula and posterior cingulate cortex. Our study may better our understanding of the neurobiological consequences of smoking. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095935 Wed, 03 Aug 2011 23:00:00 +0100 5095935 http://www.medworm.com/index.php?rid=5095934&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00361.x ABSTRACTSubstance abusers, including cocaine abusers, discount delayed rewards to a greater extent than do matched controls. In the current experiment, individual differences in discounting of delayed rewards in rats (choice of one immediate over three delayed sucrose pellets) were assessed for associations with demand for either sucrose pellets or an intravenous dose of 0.1 mg/kg/infusion cocaine. Twenty‐four male Sprague Dawley rats were split into three groups based on sensitivity to delay to reinforcement. Then, demand for sucrose pellets and cocaine was determined across a range of fixed‐ratio values. Delay discounting was then reassessed to determine the stability of this measure over the course of the experiment. Individual differences in impulsive choice were positively assoc... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095934 Wed, 03 Aug 2011 23:00:00 +0100 5095934 http://www.medworm.com/index.php?rid=5062142&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00339.x ABSTRACTSystemic infusions of the orexigenic peptide ghrelin (GHR) increase dopamine levels within the nucleus accumbens and augment cocaine‐stimulated locomotion and conditioned place preference in rats; observations that suggest an important role for GHR and GHR receptors (GHR‐Rs) in drug reinforcement. In the present studies, we examined the development of cocaine locomotor sensitization in rats, sustaining either pharmacologic antagonism or genetic ablation of GHR‐Rs. In a pharmacologic study, adult male rats were injected (i.p.) with either 0, 3 or 6 mg/kg JMV 2959 (a GHR‐R1 receptor antagonist), and 20 minutes later, with either vehicle or 10 mg/kg cocaine HCl on each of 7 consecutive days. Rats pretreated with JMV 2959 showed significantly attenuated cocaine‐induced hy... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062142 Sun, 24 Jul 2011 23:00:00 +0100 5062142 http://www.medworm.com/index.php?rid=5062141&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00340.x In this study, 32 treatment‐seeking, nicotine‐dependent smokers viewed blocks of smoking and neutral cues alternating with rest periods during magnetic resonance imaging scanning in a 3T Siemens scanner (Siemens AG, Erlangen, Bavaria, Germany). While viewing cues or control images, participants were instructed either to ‘allow yourself to crave’ or ‘resist craving.’ Data were analyzed with FSL 4.1.5, focused on the smoking cues versus neutral cues contrast, using cluster thresholding (Z > 2.3 and corrected cluster threshold of P = 0.05) at the individual and group levels. During the Crave condition, activation was seen on the left anterior cingulated cortex (LACC), medial prefrontal cortex, left middle cingulate gyrus, bilateral posterior cingulated gyrus and bilater... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062141 Sun, 24 Jul 2011 23:00:00 +0100 5062141 http://www.medworm.com/index.php?rid=5062140&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00341.x ABSTRACTRepeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake‐promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross‐sensitization with cocaine and modafinil‐induced conditioned place preference ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062140 Sun, 24 Jul 2011 23:00:00 +0100 5062140 http://www.medworm.com/index.php?rid=5062139&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00343.x ABSTRACTStudies have indicated that the metabotropic glutamate receptor 5 (mGluR5) antagonist 6‐methyl‐2‐(phenylethynyl)‐pyridine (MPEP) decreases ethanol self‐administration, and the same receptor type was also suggested to be involved in the mechanism of action of the anti‐craving substance acamprosate. Our previous research suggested that glycine receptors (GlyRs) in the nucleus accumbens (nAc) play a major part in mediating the dopamine‐elevating properties of ethanol and are highly involved in the ethanol intake‐reducing effect of acamprosate. The aim of this study was to examine if modulation of nAc dopamine via mGluR5 antagonism or GlyR agonism is a linked or separated phenomena. The extracellular levels of dopamine as well as of the GlyR ligands, glycine, taurine an... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062139 Sun, 24 Jul 2011 23:00:00 +0100 5062139 http://www.medworm.com/index.php?rid=5062138&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00345.x ABSTRACTMetabotropic glutamate receptors (mGluRs) have been implicated in the regulation of anxiety, stress responses and the neurobehavioral effects of psychostimulants. The present study was designed to examine whether antagonizing mGluR5 or activating mGluR2/3 prevents stress‐induced reinstatement of cocaine seeking. Male Wistar rats were trained to self‐administer cocaine and then subjected to daily extinction training for 2 weeks. Subsequent exposure to 15 minutes of intermittent footshock elicited robust reinstatement of responding at the previously active lever. Both the selective mGluR5 antagonist 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]piperidine (MTEP) (0–3 mg/kg, intraperitoneally) and the selective mGluR2/3 agonist (–)‐2‐oxa‐4‐aminobicylco[3.1.0]hexa... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062138 Sun, 24 Jul 2011 23:00:00 +0100 5062138 http://www.medworm.com/index.php?rid=5062137&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00346.x This study confirms the association between rs6454674 and CD. However, because there is considerable co‐morbidity of CD with other drugs of abuse, additional studies are necessary to determine whether polymorphisms in CNR1 induce a general susceptibility to substance dependence or are specific to cocaine addiction. Furthermore, as this population consists of American individuals of African descent, the possibility of population stratification should not be excluded. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062137 Sun, 24 Jul 2011 23:00:00 +0100 5062137 http://www.medworm.com/index.php?rid=5062136&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00347.x ABSTRACTIn line with learning theories of drug addiction, drug‐related cues may be viewed as important motivators of continued drug use. They may be differentially effective depending on the context and motivational significance. The present study aimed to test the significance of different contexts in modulating alcohol‐related cue reactivity. Pictures depicting alcohol intake or its paraphernalia and pictures without any relation to alcohol intake were varied to depict physical and social contexts or different consumptive contexts associated with full/half‐full/empty alcohol beverage containers. We obtained ratings of craving, valence and arousal of the cues as well as skin conductance responses (SCRs) and startle reflex modulation measures from 21 abstinent alcohol‐dependent pat... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062136 Sun, 24 Jul 2011 23:00:00 +0100 5062136 http://www.medworm.com/index.php?rid=5062135&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00349.x ABSTRACTAdequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter‐individual variability in dose‐response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well‐characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co‐med... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062135 Sun, 24 Jul 2011 23:00:00 +0100 5062135 http://www.medworm.com/index.php?rid=5062134&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00350.x ABSTRACTAge‐related differences in various acute physiological and behavioral effects of alcohol have been demonstrated in humans and in other species. Adolescents are more sensitive to positive reinforcing properties of alcohol than adults, but the cellular mechanisms that underlie such a difference are not clearly established. We, therefore, assessed age differences in the ability of ethanol to modulate glutamatergic synaptic transmission in the mouse nucleus accumbens (NAc), a brain region importantly involved in reward mechanisms. We measured field excitatory postsynaptic potentials/population spikes (fEPSP/PS) in NAc slices from adolescent (22–30 days old) and adult (5–8 months old) male mice. We found that 50 mM ethanol applied in the perfusion solution inhibits glutamatergic... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062134 Sun, 24 Jul 2011 23:00:00 +0100 5062134 http://www.medworm.com/index.php?rid=5062133&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00351.x In conclusion, we show that improved reversal learning in 5‐HTT−/− rats reflects a pre‐existing trait that is preserved during cocaine‐withdrawal. As 5‐HTT−/− rodents model the low activity s‐allele of the human serotonin transporter‐linked polymorphic region, these findings may have heuristic value in the treatment of s‐allele cocaine addicts. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062133 Sun, 24 Jul 2011 23:00:00 +0100 5062133 http://www.medworm.com/index.php?rid=5050400&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00316.x ABSTRACTPrevious neuroimaging studies have documented the structural damage in heroin addicts. However, little research has detailed the white matter microstructural changes in the human brain as a result of chronic heroin use and importantly, whether such changes can be recovered after short‐term abstinence. Decreased fractional anisotropy values in frontal cortex were found in heroin users after 3 days of abstinence in comparison with controls. However, no significant difference was found between these heroin addicts and controls after 1‐month abstinence. These results might better our understanding of the biological basis of drug addiction and provide insight into addiction treatment. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050400 Sun, 17 Jul 2011 23:00:00 +0100 5050400 http://www.medworm.com/index.php?rid=5050399&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00329.x ABSTRACTCocaine‐induced neuroadaptation of stress‐related circuitry and increased access to cocaine each putatively contribute to the transition from cocaine use to cocaine dependence. The present study tested the hypothesis that rats receiving extended versus brief daily access to cocaine would exhibit regional differences in levels of the stress‐regulatory neuropeptide corticotropin‐releasing factor (CRF). A secondary goal was to explore how CRF levels change in relation to the time since cocaine self‐administration. Male Wistar rats acquired operant self‐administration of cocaine and were assigned to receive daily long access (6 hours/day, LgA, n = 20) or short access (1 hour/day, ShA, n = 18) to intravenous cocaine self‐administration (fixed ratio 1, ∼0.50 mg/... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050399 Sun, 17 Jul 2011 23:00:00 +0100 5050399 http://www.medworm.com/index.php?rid=5050398&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00335.x ABSTRACTA relatively small percentage of humans who are exposed to drugs of abuse eventually become addicted to or dependent on those drugs. These individual differences in likelihood of developing drug addiction may reflect behavioral, neurobiological or genetic correlates of drug addiction and are therefore important to model. Behavioral economic measures of demand establish functions whose overall elasticity (rate of decrease in consumption as price increases) reflects the reinforcing effectiveness of various stimuli, including drugs. Using these demand functions, we determined the reinforcing effectiveness of five drugs of abuse (cocaine, remifentanil, ketamine, methohexital and ethanol) in 10 rhesus monkeys with histories of intravenous drug‐taking. There was a continuum of reinforc... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050398 Sun, 17 Jul 2011 23:00:00 +0100 5050398 http://www.medworm.com/index.php?rid=5050397&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00336.x ABSTRACTNeuropeptide Y (NPY) and protein kinase A (PKA) have been implicated in neurobiological responses to ethanol. We have previously reported that mutant mice lacking normal production of the RIIβ subunit of PKA (RIIβ−/− mice) show enhanced sensitivity to the locomotor stimulant effects of ethanol and increased behavioral sensitization relative to littermate wild‐type RIIβ+/+ mice. We now report that RIIβ−/− mice also show increased NPY immunoreactivity in the nucleus accumbens (NAc) core and the ventral striatum relative to RIIβ+/+ mice. These observations suggest that elevated NPY signaling in the NAc and/or striatum may contribute to the increased sensitivity to ethanol‐induced behavioral sensitization that is a characteristic of RIIβ−/− mice. Consistently, NPY... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050397 Sun, 17 Jul 2011 23:00:00 +0100 5050397 http://www.medworm.com/index.php?rid=5050396&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00337.x ABSTRACTFollowing recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psychometric scores and electrophysiological measures of cognitive control. In our patient, DBS achieved normalization of addictive behavior and craving. An electrophysiological marker of error processing (the error‐related negativity) linked to anterior mid‐cingulate cortex (aMCC) functioning was altered through DBS, an effect that could be reversed by periods without stimulation. Thus, this case supports the hypothesis that DBS of the NAc could have a positive effect ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050396 Sun, 17 Jul 2011 23:00:00 +0100 5050396 http://www.medworm.com/index.php?rid=5050395&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00338.x ABSTRACTModel studies in mice indicate that the severity of alcohol withdrawal is associated with polymorphic variation and expression of the MPDZ gene. Current knowledge about variation in the human MPDZ gene is limited; however, our data indicate its potential association with alcohol dependence. The multi‐PDZ protein is an important part of the N‐methyl‐D‐aspartate (NMDA)‐dependent α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor trafficking cascade that controls glutamate‐related excitatory neurotransmission. To investigate association of variation in the NMDA‐dependent AMPA trafficking cascade with alcohol dependence, we performed a gene‐set (pathway) analysis using single nucleotide polymorphism (SNP) data from the Study of Addictio... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050395 Sun, 17 Jul 2011 23:00:00 +0100 5050395 http://www.medworm.com/index.php?rid=5095933&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00362.x ABSTRACTAmphetamine treatment during adolescence causes long‐term cognitive deficits in rats. Pleiotrophin (PTN) is a cytokine with important roles in the modulation of synaptic plasticity, whose levels of expression are significantly regulated by amphetamine administration. To test the possibility that the long‐term consequences of periadolescent amphetamine treatment cross species and, furthermore, to test the hypothesis that PTN could be one of the factors involved in the adult cognitive deficits observed after periadolescent amphetamine administrations, we comparatively studied the long‐term consequences of periadolescent amphetamine treatment (3 mg/kg intraperitoneal, daily during 10 days) in normal wild‐type (PTN+/+) and in PTN genetically deficient (PTN−/−) mice. Withi... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5095933 Thu, 30 Jun 2011 23:00:00 +0100 5095933 http://www.medworm.com/index.php?rid=5062132&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00352.x This study is the first demonstrating that, in line with previous suggestions, cue induced activation of the mesocorticolimbic reward system triggers focusing attention to substance‐associated cues. However, this association could also be bidirectional with the attentional bias enhancing cue‐induced neural activity. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5062132 Thu, 30 Jun 2011 23:00:00 +0100 5062132 http://www.medworm.com/index.php?rid=5050394&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00344.x ABSTRACTThe paraventricular nucleus (PVN) in the hypothalamus is the main integration site that controls the hypothalamic–pituitary–adrenal (HPA) neuroendocrine stress system. Disruption of this system has been linked with alcoholism, but the specific role of the PVN has not been fully explored. Of particular interest is the ability of γ‐aminobutyric acid type A receptors (GABAARs) in the PVN, to regulate ethanol self‐administration behavior, as these receptors appear to play an essential role in mediating the effects of ethanol in the central nervous system and in the regulation of PVN activity. We observed that Long–Evans rats, in the intermittent access to 20% ethanol paradigm, consumed high amounts of ethanol and subsequently developed ethanol dependence. Microinjection of t... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=5050394 Thu, 30 Jun 2011 23:00:00 +0100 5050394 http://www.medworm.com/index.php?rid=4753602&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00318.x The objective of this study was to investigate the long‐term effects of early MD [24 hours at postnatal day (PND) 9] and/or an adolescent chronic treatment with the cannabinoid agonist CP‐55,940 (0.4 mg/kg, PND 28–42) on diverse behavioural and physiological responses of adult male and female Wistar rats. We tested them in the prepulse inhibition (PPI) of the startle response and analysed their exploratory activity (holeboard) and anxiety (elevated plus maze, EPM). In addition, we evaluated their adrenocortical reactivity in response to stress and plasma leptin levels. Maternal behaviour was measured before and after deprivation. MD induced a transient increase of maternal behaviour on reuniting. In adulthood, maternally deprived males showed anxiolytic‐like behaviour (or increas... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753602 Mon, 25 Apr 2011 23:00:00 +0100 4753602 http://www.medworm.com/index.php?rid=4753601&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00314.x ABSTRACTThe cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine‐seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self‐administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212‐2, a CB1/2 agonist, on intravenous nicotine self‐administration under fixed‐ratio (FR) and progressive‐ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212‐2 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212‐2 on nicotine‐ and cue‐induced reinstatement of nicotine seeking w... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753601 Mon, 25 Apr 2011 23:00:00 +0100 4753601 http://www.medworm.com/index.php?rid=4753600&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00319.x ABSTRACTEnvironmental stimuli repeatedly associated with the self‐administered drugs may acquire motivational importance. Because dopamine (DA) D2/D3 partial agonists and D3 antagonists interfere with the ability of drug‐associated cues to induce drug‐seeking behaviour, the present study investigated whether bifeprunox, 7‐[4‐([1,1′biphenyl]‐3‐ylmethyl)‐1‐piperazinyl]‐2(3H)‐benzoxazolone mesylate), a high‐affinity partial agonist of the D2 subfamily of DA receptors and of serotonin1A receptors, influences reinstatement of drug‐associated cue‐induced nicotine‐seeking behaviour. The study also explored whether bifeprunox reduced motivated behaviour by evaluating its effects on reinstatement induced by stimuli conditioned to sucrose. To verify whether bifeprunox... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753600 Mon, 25 Apr 2011 23:00:00 +0100 4753600 http://www.medworm.com/index.php?rid=4753599&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00322.x ABSTRACTTobacco smoking is a major risk factor for most of the diseases leading in mortality. Nicotine dependence (ND), which sustains regular smoking, is now acknowledged to be under substantial genetic control with some environmental contribution. At present, however, genetic studies on ND are mostly conducted in populations that have been poorly characterized with regard to ND‐related phenotypes for the simple reason that the respective populations were not primarily collected to study ND. The German multi‐centre study ‘Genetics of Nicotine Dependence and Neurobiological Phenotypes’, which is funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Priority Program (Schwerpunktprogramm) SPP1226: ‘Nicotine—Molecular and Physiological Effe... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753599 Mon, 25 Apr 2011 23:00:00 +0100 4753599 http://www.medworm.com/index.php?rid=4753598&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00323.x ABSTRACTThe genetic, epigenetic and environmental factors may influence the risk for neuropsychiatric disease through their effects on gene transcription. Mechanistically, these effects may be integrated through regulation of methylation of CpG dinucleotides overlapping with single‐nucleotide polymorphisms (SNPs) associated with a disorder. We addressed this hypothesis by analyzing methylation of prodynorphin (PDYN) CpG‐SNPs associated with alcohol dependence, in human alcoholics. Postmortem specimens of the dorsolateral prefrontal cortex (dl‐PFC) involved in cognitive control of addictive behavior were obtained from 14 alcohol‐dependent and 14 control subjects. Methylation was measured by pyrosequencing after bisulfite treatment of DNA. DNA binding proteins were analyzed by electr... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753598 Mon, 25 Apr 2011 23:00:00 +0100 4753598 http://www.medworm.com/index.php?rid=4753597&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00325.x ABSTRACTThe functional integrity of the nucleus accumbens (NAC) core and shell is necessary for contextual cocaine‐seeking behavior in the reinstatement animal model of drug relapse; however, the neuropharmacological mechanisms underlying this phenomenon are poorly understood. The present study evaluated the contribution of metabotropic glutamate receptor subtype 1 (mGluR1) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptor populations to drug context‐induced reinstatement of cocaine‐seeking behavior. Rats were trained to lever press for un‐signaled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine‐seeking behavior (non‐reinforced active lever pressing) was then assessed in the pr... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753597 Mon, 25 Apr 2011 23:00:00 +0100 4753597 http://www.medworm.com/index.php?rid=4753596&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00327.x ABSTRACTGenetic aspects of alcoholism have been modeled using rats selectively bred for extremes of alcohol preference and voluntary alcohol intake. These lines show similar alcohol drinking phenotypes but have different genetic and environmental backgrounds and may therefore display diverse behavioral traits as seen in human alcoholics. The multivariate concentric square field™ (MCSF) test is designed to provoke exploration and behaviors associated with risk assessment, risk taking and shelter seeking in a novel environment. The aim was to use the MCSF to characterize behavioral profiles in rat lines from selective breeding programs in the United States (P/NP, HAD1/LAD1, HAD2/LAD2), Italy (sP/sNP) and Finland (AA/ANA). The open field and elevated plus maze tests were used as reference t... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753596 Mon, 25 Apr 2011 23:00:00 +0100 4753596 http://www.medworm.com/index.php?rid=4753595&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00330.x ABSTRACTN‐acetylcysteine (NAC) has been suggested to have therapeutic potential in the treatment of drug addiction through its effects on brain glutamate homeostasis. Here we show that NAC treatment resulted in dose‐dependent reductions in cocaine seeking at both early and late stages of acquisition and maintenance of cocaine‐seeking behavior, while confirming it had no effect on cocaine reinforcement. The results indicate that NAC is able to significantly diminish the propensity to seek cocaine early and late in the development of addiction and, taken together with previous work, indicates significant potential in relapse prevention. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753595 Mon, 25 Apr 2011 23:00:00 +0100 4753595 http://www.medworm.com/index.php?rid=4733910&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00313.x ABSTRACTThe mu‐opioid receptor encoded by the gene OPRM1 plays a primary role in opiate, alcohol, cocaine and nicotine addiction. Studies using opioid antagonists demonstrate that the mu‐opioid receptor (MOP‐r) also mediates the hypothalamic–pituitary–adrenal (HPA) axis stress response. A common polymorphism in exon one of the MOP‐r gene, A118G, has been shown to significantly alter receptor function and MOP‐r gene expression; therefore, this variant likely affects HPA‐axis responsivity. In the current study, we have investigated whether the presence of the 118AG variant genotype affects HPA axis responsivity to the stressor metyrapone, which transiently blocks glucocorticoid production in the adrenal cortex. Forty‐eight normal and healthy volunteers (32 men, 16 women) we... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733910 Tue, 19 Apr 2011 23:00:00 +0100 4733910 http://www.medworm.com/index.php?rid=4733909&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00315.x ABSTRACTGiven that social influences are among the strongest predictors of adolescents' drug use, this study examines the effects of social interactions on morphine sensitization in both adolescent and adult rats. Rats treated with morphine (twice daily, 6 days, 2.5–10 mg/kg, subcutaneously, s.c.) or saline were group‐housed in two different conditions. Thus, four experimental groups were examined for each age group: (1) morphine‐treated rats housed physically and visually separate from saline‐injected rats (‘morphine only’); (2) morphine‐treated rats housed together with saline‐injected rats (‘morphine cage‐mates’); (3) saline‐injected rats housed together with morphine‐treated rats (‘saline cage‐mates’); and (4) saline‐injected rats housed physically a... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733909 Tue, 19 Apr 2011 23:00:00 +0100 4733909 http://www.medworm.com/index.php?rid=4733908&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00317.x ABSTRACTThe dopamine (DA) D3 receptor is posited to be importantly involved in drug reward and addiction, and D3 receptor antagonists have shown extraordinary promise as potential anti‐addiction pharmacotherapeutic agents in animal models of drug addiction. SB‐277011A is the best characterized D3 receptor antagonist in such models. However, the potential use of SB‐277011A in humans is precluded by pharmacokinetic and toxicity problems. We here report a novel D3 receptor antagonist YQA14 that shows similar pharmacological properties as SB‐277011A. In vitro receptor binding assays suggest that YQA14 has two binding sites on human cloned D3 receptors with Ki‐High (0.68 × 10−4 nM) and Ki‐Low (2.11 nM), and displays > 150‐fold selectivity for D3 over D2 receptors a... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733908 Tue, 19 Apr 2011 23:00:00 +0100 4733908 http://www.medworm.com/index.php?rid=4733907&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00320.x ABSTRACTWhile there is solid evidence that cannabis use is heritable, attempts to identify genetic influences at the molecular level have yielded mixed results. Here, a large twin family sample (n = 7452) was used to test for association between 10 previously reported candidate genes and lifetime frequency of cannabis use using a gene‐based association test. None of the candidate genes reached even nominal significance (P < 0.05). The lack of replication may point to our limited understanding of the neurobiology of cannabis involvement and also to potential publication bias and false‐positive findings in previous studies. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733907 Tue, 19 Apr 2011 23:00:00 +0100 4733907 http://www.medworm.com/index.php?rid=4733906&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00321.x In this study, we examined the association of this polymorphism with alcohol dependence. Subject–control analysis included 206 alcohol‐dependent and 168 control subjects. Average observed repeat numbers and genotype distributions were significantly different (P‐value = 0.001) in alcohol‐dependent subjects versus control subjects. Short alleles were significantly less frequent among alcohol‐dependent subjects (odds ratio = 0.58, P‐value = 7 × 10−4). These results could be replicated in an independent sample of 116 alcohol‐dependent subjects. For the first time, a significant association was identified between this polymorphism and alcoholism. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733906 Tue, 19 Apr 2011 23:00:00 +0100 4733906 http://www.medworm.com/index.php?rid=4733905&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00324.x We examined varenicline effects on emotional processing in 25 abstinent smokers after 13 days of varenicline and placebo using a within‐subject cross‐over design. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging was acquired while subjects completed a face emotion identification task. Results showed a significant drug effect, characterized by decreased BOLD signal in dorsal anterior cingulate/medial frontal cortex, occipital cortex and thalamus. Increased BOLD signal was observed in the middle temporal gyrus. Varenicline improved correct response time; however, neither BOLD signal nor performance effects were moderated by emotion type. An exploratory region of interest analysis suggests that varenicline reduced amygdala activity independent of emotional valence... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733905 Tue, 19 Apr 2011 23:00:00 +0100 4733905 http://www.medworm.com/index.php?rid=4733904&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00326.x ABSTRACTMolecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5 g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1‐ and 5‐day groups) or 1, 3 or 7 days after the last administration for the three other 5‐day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up‐regulation of prodynorphin and pronociceptin was observed in the 1‐day group; moreover, pronociceptin and... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733904 Tue, 19 Apr 2011 23:00:00 +0100 4733904 http://www.medworm.com/index.php?rid=4733903&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00333.x ABSTRACTThe α4βδ gamma‐aminobutyric acid A receptor (GABAAR) has been proposed to mediate the rewarding effects of low‐to‐moderate concentrations of alcohol (ethanol) that approximate those achieved by social drinking. If this is true, then this receptor should be necessary for the reinforcing effects of ethanol as assessed in an instrumental self‐administration procedure in which rats are trained to lever press for oral ethanol. We used viral‐mediated RNA interference to transiently reduce expression of the α4 GABAAR subunit in the shell region of the nucleus accumbens (NAc). We found that responding for ethanol was significantly reduced after α4 reductions in the NAc shell, but not NAc core. This reduction was specific to ethanol, as responding for sucrose was not altered.... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733903 Tue, 19 Apr 2011 23:00:00 +0100 4733903 http://www.medworm.com/index.php?rid=4704539&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00298.x ABSTRACTHigh blood–brain permeability and effective delivery of morphine to the brain have been considered as explanations for the high potency of heroin. Results from Andersen et al. indicate that 6‐monoacetylmorphine (6‐MAM), and not morphine, is the active metabolite responsible for the acute effects observed for heroin. Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6‐MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice. The estimated pharmacokinetic parameters imply that the very low heroin and the high 6‐MAM levels observed both in blood and brain in the original experiment are likely to be caused by a very high metabolic rate of heroin in blood. The ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4704539 Sun, 10 Apr 2011 23:00:00 +0100 4704539 http://www.medworm.com/index.php?rid=4893278&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00342.x ABSTRACTIt is well known that melatonin participates in the regulation of many important physiological functions such as sleep–wakefulness cycle, motor coordination and neural plasticity, and cognition. However, as there are contradictory results regarding the melatonin production diurnal profile under alcohol consumption, the aim of this paper was to study the phenomenology and mechanisms of the putative modifications on the daily profile of melatonin production in rats submitted to chronic alcohol intake. The present results show that rats receiving 10% ethanol in drinking water for 35 days display an altered daily profile of melatonin production, with a phase delay and a reduction in the nocturnal peak. This can be partially explained by a loss of the daily rhythm and the 25% reductio... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4893278 Thu, 31 Mar 2011 23:00:00 +0100 4893278 http://www.medworm.com/index.php?rid=4794794&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00328.x ABSTRACTCompulsion in alcohol use disorders (AUD) has been attributed to impairment in response inhibition. Because genes that regulate dopamine (DA) have been implicated not only for risk for AUD but also for impulsivity based on behavioral studies, we set out to examine the underlying neural mechanisms associated with these effects. We collected functional magnetic resonance imaging images on 53 heavy drinking but otherwise healthy adults while performing the Go/NoGo task. We predicted that genetic variants previously reported in the literature to be associated with substance abuse, specifically the DRD2 rs1799732 and DRD4 VNTR, will modulate neural processes underlying response inhibition. Our results showed differential neural response for the DRD4 VNTR during successful inhibition in ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4794794 Thu, 31 Mar 2011 23:00:00 +0100 4794794 http://www.medworm.com/index.php?rid=4753594&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00331.x ABSTRACTFew studies have investigated whether genetic abnormalities predispose individuals to heavy betel quid (BQ) use. One of the major ingredients of BQ, arecoline, is known to affect the expression of monoamine oxidase A (MAO‐A). We investigated the extent to which arecoline inhibits MAO‐A expression and the role of MAO‐A polymorphisms in BQ use in Taiwanese aborigines. Cytotoxicity assays, microarrays and quantitative reverse transcriptase‐polymerase chain reaction were used to examine the effects of arecoline and areca nut extract (ANE) on cell viability and MAO‐A expression in neuroblastoma SH‐SY5Y cells. After identifying the effective concentrations of arecoline and ANE in vitro, we examined the in vivo effects of these compounds using a rat model system. Our results i... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4753594 Thu, 31 Mar 2011 23:00:00 +0100 4753594 http://www.medworm.com/index.php?rid=4733902&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00334.x ABSTRACTDrug reinforcement learning is relevant for the development of addiction. The present study investigated how changes in the magnitude of drug‐unconditioned stimulus during associative learning modulate the acquisition and extinction of cocaine‐induced conditioned place preference (CPP). B6;129S F2 mice were conditioned by three dosing schedules of cocaine: (1) ascending, (2) fixed and (3) descending daily doses. Following acquisition of CPP, extinction was induced by (1) context re‐exposure, (2) reconditioning by saline and (3) reconditioning by descending doses of cocaine. The magnitude of CPP following conditioning by daily ascending doses of cocaine (2, 4, 8 and 16 mg/kg) was significantly higher than that obtained from conditioning by either a fixed daily dose (16 mg/... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4733902 Thu, 31 Mar 2011 23:00:00 +0100 4733902 http://www.medworm.com/index.php?rid=4704538&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00312.x ABSTRACTFrequent and excessive tanning persists despite a growing understanding of its associated morbidity and mortality, suggesting that ultraviolet radiation may impart rewarding effects beyond the assumed cosmetic benefits. To empirically measure putative centrally rewarding properties of ultraviolet radiation (UVR), we assessed the effects of a commercially available tanning bed upon regional cerebral blood flow (rCBF), a measure of brain activity, using single‐photon emission computed tomography (SPECT). Seven frequent salon bed tanners were placed under a UVA/UVB tanning light during two sessions; one session with UVR and the other with filtered UVR (sham UVR). Session order was randomized and subjects were blinded to study order. During the UVR session, relative to sham UVR sessi... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4704538 Thu, 31 Mar 2011 23:00:00 +0100 4704538 http://www.medworm.com/index.php?rid=4574987&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00311.x ABSTRACTThe mammalian target of rapamycin (mTOR) is a serine‐threonine kinase that controls global protein synthesis, in part, by modulating translation initiation, a rate‐limiting step for many mRNAs. Previous studies implicate mTOR in regulating stimulant‐induced sensitization and antidepressive‐like behavior in rodents, as well as drug craving in abstinent heroin addicts. To determine if signaling downstream of mTOR is affected by repeated cocaine administration in reward‐associated brain regions, and if inhibition of mTOR alters cocaine‐induced behavioral plasticity, C57BL/6J mice received four intraperitoneal (i.p.) injections of 15 mg/kg cocaine and levels of phosphorylated P70S6 kinase and ribosomal S6 protein—two translational regulators directly downstream of mTOR�... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574987 Sat, 12 Mar 2011 05:15:25 +0100 4574987 http://www.medworm.com/index.php?rid=4574997&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00301.x ABSTRACTNicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers' brains have smaller cortical grey matter volumes and/or lower densities compared with non‐smokers'. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community‐based sample of ‘young–old’ individuals. Brain volumes were measured using a semi‐automated method in 315 participants aged ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574997 Fri, 11 Mar 2011 00:00:00 +0100 4574997 http://www.medworm.com/index.php?rid=4574996&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00302.x ABSTRACTP50 gating is a major functional biomarker in research on schizophrenia and other psychiatric conditions with high smoking prevalence. It is used as endophenotype for studying nicotinic systems genetics and as surrogate endpoint measure for drug development of nicotinic agonists. Surprisingly, little is known about P50 gating in the general population and the relationship to smoking‐related characteristics. In this multicenter study at six academic institutions throughout Germany, n = 907 never‐smokers (NS < 20 cigarettes/lifetime), n = 463 light smokers (LS) with Fagerström Test for Nicotine Dependence (FTND) ≥ 4 and n = 353 heavy smokers (HS, FTND < 4) were randomly selected from the general population. As part of a standardized protocol for i... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574996 Fri, 11 Mar 2011 00:00:00 +0100 4574996 http://www.medworm.com/index.php?rid=4574995&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00303.x ABSTRACTCurrently, there are no existing procedures that model in animals the situation where exposure to prolonged mild food restriction results in relapse to drug abuse. Here, reinstatement of extinguished heroin‐seeking behavior was assessed in rats under extinction conditions. Ten, but not 7, days of food restriction (∼80% of sated body weight) induced reinstatement of heroin seeking, over and above the spontaneous recovery of the behavior. It is suggested that chronic, mild, food restriction following extinction of drug seeking behavior might serve as a useful model to study the increased risk for relapse to drug abuse due to dietary challenges. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574995 Fri, 11 Mar 2011 00:00:00 +0100 4574995 http://www.medworm.com/index.php?rid=4574994&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00304.x ABSTRACTAlcoholism is characterized by a progressive loss of control over ethanol intake. The purpose of this study was to identify transcriptional changes selectively associated with excessive ethanol drinking in dependent mice, as opposed to non‐dependent mice maintaining a stable voluntary consumption or mice solely undergoing forced intoxication. We measured expression levels of 106 candidate genes in the extended amygdala, a key brain structure for the development of drug addiction. Cluster analysis identified 17 and 15 genes selectively induced or repressed, respectively, under conditions of excessive drinking. These genes belong to signaling pathways involved in neurotransmission and transcriptional regulation. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574994 Fri, 11 Mar 2011 00:00:00 +0100 4574994 http://www.medworm.com/index.php?rid=4574993&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00306.x ABSTRACTThe present study was undertaken to identify possible similarities between the effects of kappa‐opioid receptor agonist, N‐methyl‐D‐aspartate‐receptor antagonist, and sigma receptor agonist on the discriminative stimulus effects of U‐50488H, and the possible involvement of sigma receptors in the discriminative stimulus and aversive effects of U‐50488H. The kappa‐opioid receptor agonist U‐50488H produced significant place aversion as measured by the conditioned place preference procedure, and this effect was completely abolished by treatment with the putative sigma‐1 receptor antagonist NE‐100. In addition, phencyclidine (+)‐SKF‐10047 and (+)‐pentazocine, which are sigma receptor agonists, generalized to the discriminative stimulus effects of U‐50488H i... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574993 Fri, 11 Mar 2011 00:00:00 +0100 4574993 http://www.medworm.com/index.php?rid=4574992&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00305.x ABSTRACTThe influence of friends and peers is theoretically one of the most consistent and important factors explaining adolescent alcohol use. However, not all adolescents are equally likely to be influenced by their friends' drinking behaviors. Genetic factors may underlie these inter‐individual differences in susceptibility to the drinking behavior of friends. Because the long allele (≥ 7 repeats) of the dopamine D4 receptor (DRD4) gene has been associated with susceptibility to alcohol and alcohol‐related cues, we tested whether associations between best friend's and adolescent's alcohol use differed for DRD4 genotypes. A Dutch nationwide sample of 308 adolescents (age 13 at baseline) participated in a prospective, community‐based study with five annual waves. A cross‐lagge... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574992 Fri, 11 Mar 2011 00:00:00 +0100 4574992 http://www.medworm.com/index.php?rid=4574991&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00307.x ABSTRACTWe investigated the Cytosin‐phosphatidyl‐Guanin (CpG) island promoter methylation (mean and methylation of individual CpG‐sites) of the nerve growth factor (NGF) gene in the blood of alcohol‐dependent patients (57 male patients) during withdrawal (days 1, 7 and 14). Methylation and NGF serum levels did not change significantly from days 1–7. From days 7–14, mean methylation increased (F = 30.55, P < 0.001), whereas the NGF serum levels decreased significantly (days 7–14: F = 17.95, P < 0.001). The NGF serum levels were significantly associated with the mean methylation of the investigated CpG‐sites (F = 1.55, P < 0.001). These results imply an epigenetic regulation of the NGF gene during alcohol withdrawal. (Source: Addiction Biology... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574991 Fri, 11 Mar 2011 00:00:00 +0100 4574991 http://www.medworm.com/index.php?rid=4574990&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00308.x ABSTRACTAnimal studies suggest that the gut‐brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics.This investigation consisted of two studies. Study 1 was a 12‐week study with alcohol‐dependent subjects, where plasma ghrelin determinations were assessed four times (T0‐T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case‐control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol‐depen... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574990 Fri, 11 Mar 2011 00:00:00 +0100 4574990 http://www.medworm.com/index.php?rid=4574989&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00309.x ABSTRACTAlcohol and nicotine use disorders are often treated as separate diseases, despite evidence that approximately 80–90% of alcohol dependent individuals are also heavy smokers. Both nicotine and ethanol have been shown to interact with neuronal nicotinic acetylcholine receptors (nAChRs), suggesting these receptors are a common biological target for the effects of nicotine and ethanol in the brain. There are few studies that have examined the effects of co‐administered nicotine and ethanol on the activity of nAChRs in rodents. In the present study, we show that Sprague‐Dawley rats, a strain often used for nicotine studies but not as often for voluntary ethanol intake studies, will consume 20% ethanol using both the intermittent‐access two‐bottle‐choice and operant self‐a... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574989 Fri, 11 Mar 2011 00:00:00 +0100 4574989 http://www.medworm.com/index.php?rid=4574988&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00310.x In conclusion, these findings support a specific regulatory role for mGluR7 on alcohol drinking and preference and provide evidence for the use of AMN082‐type drugs as potential new treatments for alcohol‐use disorders in man. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4574988 Fri, 11 Mar 2011 00:00:00 +0100 4574988 http://www.medworm.com/index.php?rid=4544894&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2011.00332.x (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4544894 Fri, 04 Mar 2011 12:08:41 +0100 4544894 http://www.medworm.com/index.php?rid=4544893&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00300.x ABSTRACTRecent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4544893 Fri, 04 Mar 2011 12:08:40 +0100 4544893 http://www.medworm.com/index.php?rid=4470389&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00278.x ABSTRACTBaclofen, a γ‐amino‐butyric‐acid (GABA)B receptor agonist, can reduce cue‐enhanced cocaine‐seeking in rats and attenuate cue‐evoked craving in cocaine addicts. However, baclofen also has sedative effects that might interfere with its efficacy in reducing cocaine's rewarding effects. The present study aimed at comparing the effects of baclofen with the GABAB‐receptor positive allosteric modulator GS39783 on psychostimulant conditioned cues. Two identically trained groups of male Lister‐Hooded rats were baselined on a new responding for a light stimulus previously paired with cocaine self‐administration. One group was treated with the GABAB‐receptor positive allosteric modulator GS39783 (0, 10, 30, 100 mg/kg, i.p.), the other with baclofen (0, 0.6, 1.25, 1.9, 2... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470389 Fri, 11 Feb 2011 00:00:00 +0100 4470389 http://www.medworm.com/index.php?rid=4470388&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00279.x In conclusion, plasma IgG, IgA and IgM antibodies binding specifically to PEth were found in subjects of all study groups. Subjects with heavy alcohol consumption showed markedly lower plasma immunoglobulin levels to PEth, potentially making them useful as a biomarker to distinguish heavy from moderate alcohol use. (Source: Addiction Biology) Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470388 Fri, 11 Feb 2011 00:00:00 +0100 4470388 http://www.medworm.com/index.php?rid=4470387&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00280.x ABSTRACTThe mechanisms involved in alcohol use disorders are complex. It has been shown that ghrelin is an important signal for the control of body weight homeostasis, preferably by interacting with hypothalamic circuits, as well as for drug reward by activating the mesolimbic dopamine system. The ghrelin receptor (GHS‐R1A) has been shown to be required for alcohol‐induced reward. Additionally, ghrelin increases and GHR‐R1A antagonists reduce moderate alcohol consumption in mice, and a single nucleotide polymorphism in the GHS‐R1A gene has been associated with high alcohol consumption in humans. However, the role of central ghrelin signaling in high alcohol consumption is not known. Therefore, the role of GHS‐R1A in operant self‐administration of alcohol in rats as well as for ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470387 Fri, 11 Feb 2011 00:00:00 +0100 4470387 http://www.medworm.com/index.php?rid=4470386&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00282.x ABSTRACTThe synaptic signaling mechanisms mediating the behavioral effects of ethanol (EtOH) remain poorly understood. Post‐synaptic density 95 (PSD‐95, SAP‐90, Dlg4) is a key orchestrator of N‐methyl‐D‐aspartate receptors (NMDAR) and glutamatergic synapses, which are known to be major sites of EtOH's behavioral actions. However, the potential contribution of PSD‐95 to EtOH‐related behaviors has not been established. Here, we evaluated knockout (KO) mice lacking PSD‐95 for multiple measures of sensitivity to the acute intoxicating effects of EtOH (ataxia, hypothermia, sedation/hypnosis), EtOH drinking under conditions of free access and following deprivation, acquisition and long‐term retention of EtOH conditioned place preference (CPP) (and lithium chloride‐induced c... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470386 Fri, 11 Feb 2011 00:00:00 +0100 4470386 http://www.medworm.com/index.php?rid=4470385&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00283.x ABSTRACTA great number of studies have shown the presence of physiological interactions between brain neurotransmitter systems in behavioural responses. This is the case for opioid, cholecystokinin (CCK) and dopamine systems. However, so far the role that the CCK system may play in vulnerability to consumption of drugs of abuse is not clear. This was investigated in this study using Lewis rats that are more sensitive to the reinforcing properties of drugs of abuse than Fischer rats. The extraneuronal CCK8 levels and brain CCK2 receptors were found higher in Fischer than in Lewis rats in the nucleus accumbens, one of the most important structures involved in drug consumption. Moreover, pharmacological modulation of the CCK system by administration of a selective CCK2 agonist blocked, in the... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470385 Fri, 11 Feb 2011 00:00:00 +0100 4470385 http://www.medworm.com/index.php?rid=4470384&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00284.x ABSTRACTAnalysis of mouse brain gene expression, using strains that differ in alcohol consumption, provided a number of novel candidate genes that potentially regulate alcohol consumption. We selected six genes [beta‐2‐microglobulin (B2m), cathepsin S (Ctss), cathepsin F (Ctsf), interleukin 1 receptor antagonist (Il1rn), CD14 molecule (Cd14) and interleukin 6 (Il6)] for behavioral validation using null mutant mice. These genes are known to be important for immune responses but were not specifically linked to alcohol consumption by previous research. Null mutant mice were tested for ethanol intake in three tests: 24‐hour two‐bottle choice, limited access two‐bottle choice and limited access to one bottle of ethanol. Ethanol consumption and preference were reduced in all the null m... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470384 Fri, 11 Feb 2011 00:00:00 +0100 4470384 http://www.medworm.com/index.php?rid=4470383&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00285.x ABSTRACTLittle is known how social interaction, if offered as an alternative to drug consumption, affects neural circuits involved in drug reinforcement and substance dependence. Conditioned place preference (CPP) for cocaine (15 mg/kg i.p.) or social interaction (15 minutes) as an alternative stimulus was investigated in male Sprague‐Dawley rats. Four social interaction episodes with a male adult conspecific completely reversed cocaine CPP and were even able to prevent reacquisition of cocaine CPP. Social interaction also reversed cocaine CPP‐induced expression of the immediate‐early gene zif268 in the nucleus accumbens shell, the central and basolateral amygdala and the ventral tegmental area. These findings suggest that social interaction, if offered in a context that is clearly... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470383 Fri, 11 Feb 2011 00:00:00 +0100 4470383 http://www.medworm.com/index.php?rid=4470382&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00289.x ABSTRACTIn rodents, a conditioned place preference (CPP) can be induced by morphine. In the current study, we designed a biased place conditioning paradigm to test the rewarding effects of morphine in freely moving rhesus monkeys. Five monkeys were first placed in three serial rooms with the doors open between them for three days. After this habituation period, during which baseline preference for each of the two end rooms was measured, CPP conditioning occurred when the monkeys were injected intramuscularly with morphine at an increasing dose (1.5, 3, 4.5 mg/kg) before they entered the non‐preferred room and on alternate days, with saline before they entered the preferred room. Morphine and saline treatment lasted for six days, respectively. CPP was tested 24 hours after the end of CP... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470382 Fri, 11 Feb 2011 00:00:00 +0100 4470382 http://www.medworm.com/index.php?rid=4470381&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00290.x ABSTRACTPre‐clinical research indicates that opioids reduce extracellular glutamate in acute opioid treatment, whereas during withdrawal, glutamatergic neurotransmission is increased and withdrawal symptoms can be blocked by glutamate receptor antagonists. The glutamate hypothesis of addiction suggests that withdrawal‐associated hyperglutamatergic states destabilize the glutamatergic system chronically and contribute to relapse. magnetic resonance spectroscopy at three tesla optimized for glutamate assessment (TE 80 ms) was performed in the anterior cingulate gyrus (ACC) and frontal white matter (fWM) of 17 opiate‐dependent patients during opiate maintenance therapy and 20 healthy controls. Controlling for age and gray matter content, glutamate in the ACC was positively associated ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470381 Fri, 11 Feb 2011 00:00:00 +0100 4470381 http://www.medworm.com/index.php?rid=4470380&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00291.x ABSTRACTAlcoholism is a devastating condition that represents a progression from initial alcohol use to dependence. Although most individuals are capable of consuming alcohol in a limited fashion, the development of alcohol dependence in a subset of individuals is often associated with negative emotional states (including anxiety and depression). Since the alleviation of this negative motivational state via excessive alcohol consumption often becomes a central goal of alcoholics, the transition from initial use to dependence is postulated to be associated with a transition from positive to negative reinforcement mechanisms. Vasopressin is a neuropeptide known to potentiate the effects of CRF on the HPA axis, and emerging evidence also suggests a role for centrally located vasopressin actin... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470380 Fri, 11 Feb 2011 00:00:00 +0100 4470380 http://www.medworm.com/index.php?rid=4470379&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00292.x ABSTRACTHuman and animal research indicates that females may have a higher biological propensity for cocaine abuse than do males. Furthermore, reproductive status modulates the subjective effects of cocaine in women and self‐administration rates in rats. Despite the attention that has been given to the modulation of appetitive responses by reproductive status and the well‐known mixed positive and negative subjective effects of cocaine, it is unknown if similar effects are observed on aversive responses to cocaine. The present study examines the impact of sex and estrous cycle on approach‐avoidance behavior for cocaine as measured in the runway self‐administration model. Male and freely cycling female Sprague Dawley rats were trained to traverse a straight alley for single daily inj... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470379 Fri, 11 Feb 2011 00:00:00 +0100 4470379 http://www.medworm.com/index.php?rid=4470378&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00293.x This study was the first to examine the effects of diacetylmorphine (DAM) on peripheral SNCA protein expression along with craving in opiate‐dependent patients and to compare their NACP‐Rep1 allele lengths with those of healthy controls. Using an experimental design, opiate‐dependent patients on injectable heroin maintenance were investigated at four time points, twice pre‐ and post‐injection of DAM. SNCA protein levels of 30 DAM‐maintained patients were measured using enzyme‐linked immunosorbent assay. Participant‐rated effects were assessed in 42 patients by Tiffany's Heroin Craving Questionnaire (HCQ), Gossop's Short Opiate Withdrawal Scale and Visual Analogs. NACP‐Rep1 alleles of 42 patients and 101 controls were analyzed. One‐way repeated‐measures ANOVAs provided... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470378 Fri, 11 Feb 2011 00:00:00 +0100 4470378 http://www.medworm.com/index.php?rid=4470377&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00294.x ABSTRACTThe decision to eat is strongly influenced by non‐homeostatic factors such as food palatability. Indeed, the rewarding and motivational value of food can override homeostatic signals, leading to increased consumption and hence, obesity. Ghrelin, a gut‐derived orexigenic hormone, has a prominent role in homeostatic feeding. Recently, however, it has emerged as a potent modulator of the mesolimbic dopaminergic reward pathway, suggesting a role for ghrelin in food reward. Here, we sought to determine whether ghrelin and its receptors are important for reinforcing motivation for natural sugar reward by examining the role of ghrelin receptor (GHS‐R1A) stimulation and blockade for sucrose progressive ratio operant conditioning, a procedure used to measure motivational drive to obta... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470377 Fri, 11 Feb 2011 00:00:00 +0100 4470377 http://www.medworm.com/index.php?rid=4470376&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00295.x The objective of this study was to determine the role of DOP‐Rs in yohimbine‐stress‐induced reinstatement of ethanol‐seeking. Male, Long‐Evans rats were trained to self‐administer 10% ethanol in daily 30‐minute operant self‐administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP‐R antagonist, SoRI‐9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress‐induced reinstatement. Additionally, DOP‐R‐stimulated [35S]GTPγS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre‐treatment with SoRI‐9409 decreased yohimbine stress‐induced reinstatement of ethanol‐seeking but did not affect yohimbine�... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470376 Fri, 11 Feb 2011 00:00:00 +0100 4470376 http://www.medworm.com/index.php?rid=4470375&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00296.x ABSTRACTReexposure to cocaine‐associated environments promotes relapse to cocaine seeking and represents a persistent impediment to successful abstinence. Neurobiological adaptations are thought to underlie the preservation of drug‐seeking behavior during protracted withdrawal periods, possibly including changes associated specifically with cocaine‐paired contexts. We measured GluR1S845 and extracellular signal‐regulated kinase (ERK) phosphorylation in rat striatal subregions in an animal model of cocaine relapse. Animals with cocaine self‐administration experience and their yoked partners were exposed to extinction conditions for one hour in the drug‐paired environmental context after one day or three weeks withdrawal to measure protein phosphorylation induced by the cocaine�... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470375 Fri, 11 Feb 2011 00:00:00 +0100 4470375 http://www.medworm.com/index.php?rid=4470374&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00297.x ABSTRACTRepeated administration of psychostimulant drugs, such as amphetamine, induces an enhanced behavioral response to subsequent drug challenge. This behavioral sensitization is proposed to model the increased drug craving observed in human psychostimulant abusers. Current thinking is that the ventral tegmental area, but not the nucleus accumbens, plays a critical role in the development of behavioral sensitization. Here, we report that the concomitant blockade of glutamatergic and nicotinic ionotropic receptors in the core of the nucleus accumbens blocks the development of behavioral sensitization to amphetamine and further abolishes the increase in extracellular dopamine release induced by amphetamine in the nucleus accumbens. These findings demonstrate that the development of behavi... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470374 Fri, 11 Feb 2011 00:00:00 +0100 4470374 http://www.medworm.com/index.php?rid=4459892&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00288.x ABSTRACTWe demonstrated that the genotype of the variable number tandem repeats (VNTRs) in the linked polymorphic region (LPR) of the 5′ promoter and in the intron 2 (Stin2) transcriptional regulatory domains of the serotonin transporter SLC6A4 gene determined its promoter interactions with transcription factors and co‐activators in response to cocaine in the JAr cell line. The LPR variants contain 14 (short, s) or 16 (long, l) copies of a 22–23 bp repeat element, whereas the Stin2 VNTR exists as three variants containing 9, 10 or 12 copies of a 16–17 bp repeat. We observed a differential effect of cocaine on the association of the promoter with the transcription factor CTCF, which bound to both LPR alleles prior to cocaine exposure but only to the l‐allele following exposure... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4459892 Thu, 10 Feb 2011 00:00:00 +0100 4459892 http://www.medworm.com/index.php?rid=4532118&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00287.x We examined the available scientific literature on pharmacogenetic advancements in the field of drug addiction with a focus on alcohol and tobacco to provide a summary of genes implicated in the effectiveness of pharmacotherapy for addiction. In addition, we reviewed pharmacogenetic research on cocaine and heroin dependence. Thus far, the most promising results were obtained for polymorphisms in the OPRM1 and CYP2A6 genes, which have been effective in predicting clinical response to naltrexone in alcoholism and nicotine replacement therapy in smoking, respectively. Opinions differ as to whether pharmacogenetic testing should be implemented in the clinic at this time because clinical utility and cost‐effectiveness require further investigation. However, the data summarized in this review ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4532118 Sat, 01 Jan 2011 00:00:00 +0100 4532118 http://www.medworm.com/index.php?rid=4470373&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00299.x ABSTRACTThe present study was undertaken to examine whether genetically predetermined differences in components of the endocannabinoid system were present in the brain of Sardinian alcohol‐preferring (sP) and Sardinian alcohol‐non‐preferring (sNP) rats, a pair of rat lines selectively bred for opposite alcohol preference. The effects of acquisition and maintenance of alcohol drinking, alcohol withdrawal, and alcohol re‐exposure on the endocannabinoid system was also assessed in the striatum of sP rats. The findings revealed significantly higher density of the CB1 receptors and levels of CB1 receptor mRNA, CB1 receptor‐mediated G‐protein coupling, and endocannabinoids in the cerebral cortex, hippocampus and striatum of alcohol‐naive sP rats than sNP rats. A significantly lower... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4470373 Sat, 01 Jan 2011 00:00:00 +0100 4470373 http://www.medworm.com/index.php?rid=4459891&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00286.x ABSTRACTDual process models of addiction emphasize the importance of implicit (automatic) cognitive processes in the development and maintenance of substance use behavior. Although genetic influences are presumed to be relevant for dual process models, few studies have evaluated this possibility. The current study examined two polymorphisms with functional significance for alcohol use behavior (COMT Val158Met and ALDH2*2) in relation to automatic alcohol cognitions and tested additive and interactive effects of genotype and implicit cognitions on drinking behavior. Participants were college students (n = 69) who completed Implicit Association Tasks (IATs) designed to assess two classes of automatic drinking motives (enhancement motives and coping motives). Genetic factors did not show ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4459891 Sat, 01 Jan 2011 00:00:00 +0100 4459891 http://www.medworm.com/index.php?rid=4450226&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00277.x ABSTRACTPreviously we demonstrated profound effects of dopamine transporter (DAT) SLC6A3 genotype on limbic responses to smoking cues (SCs). Probands carrying at least one copy of the 9‐repeat allele (9‐repeat carriers) had greater neural responses to SCs in the anatomically interconnected rostral ventral striatum/medial orbitofrontal cortex (VS/mOFC), compared with homozygotes for the 10‐repeat allele (10/10‐repeats). To test the reliability of the initial findings, we examined perfusion functional magnetic resonance images acquired during SC exposure in a new cohort of smokers (N = 26) who were genotyped for the SLC6A3 polymorphism. In smokers overall, activity was enhanced in the VS/mOFC (t = 3.77). Contrasts between allelic groups revealed that 9‐repeat carriers had a... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4450226 Sat, 01 Jan 2011 00:00:00 +0100 4450226 http://www.medworm.com/index.php?rid=4285147&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00281.x ABSTRACTGlial cell line‐derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time‐dependent increases in cue‐induced cocaine‐seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self‐administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone‐light cue) and tested for cue‐induced heroin‐seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue‐induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time‐dependent increases in extinction responding were associated with time‐dependent changes in GDNF mRNA expression in VTA ... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4285147 Fri, 24 Dec 2010 05:41:26 +0100 4285147 http://www.medworm.com/index.php?rid=4285153&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00269.x ABSTRACTWe investigated possible alterations of pharmacologically‐isolated, evoked GABAA inhibitory postsynaptic potentials (eIPSPs) and miniature GABAA inhibitory postsynaptic currents (mIPSCs) in the rat central amygdala (CeA) elicited by acute application of µ‐opioid receptor (MOR) agonists (DAMGO and morphine; 1 µM) and by chronic morphine treatment with morphine pellets. The acute activation of MORs decreased the amplitudes of eIPSPs, increased paired‐pulse facilitation (PPF) of eIPSPs and decreased the frequency (but not the amplitude) of mIPSCs in a majority of CeA neurons, suggesting that acute MOR‐dependent modulation of this GABAergic transmission is mediated predominantly via presynaptic inhibition of GABA release. We observed no significant changes in the membrane p... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4285153 Thu, 23 Dec 2010 00:00:00 +0100 4285153 http://www.medworm.com/index.php?rid=4285152&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00270.x ABSTRACTMethamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication, but has not been characterized in METH use. We recorded HRV in a sample of currently abstinent individuals with a history of METH dependence compared to age‐ and gender‐matched drug‐free comparison subjects. HRV was assessed using time domain, frequency domain, and non‐linear entropic analyses in 17 previously METH‐dependent and 21 drug‐free comparison individuals during a 5 minute rest period. The METH‐dependent group demonstrated significant reduction... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4285152 Thu, 23 Dec 2010 00:00:00 +0100 4285152 http://www.medworm.com/index.php?rid=4285151&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00271.x ABSTRACTEndocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive‐valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity of eCBs (witho... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4285151 Thu, 23 Dec 2010 00:00:00 +0100 4285151 http://www.medworm.com/index.php?rid=4285150&cid=s_17944_2_f&fid=17944&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1369-1600.2010.00272.x ABSTRACTThe present study used conventional and quantitative microdialysis to assess glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the rat following a moderate‐dose ethanol treatment regimen. Male Wistar rats received 3.4 g/kg of ethanol or water for 6 days via gastric gavage. Microdialysis experiments commenced 2 days later. Basal and depolarization‐induced glutamate overflow were significantly elevated in ethanol‐treated animals. Basal and depolarization‐induced gamma‐aminobutyric acid (GABA) overflow were unaltered. Quantitative no‐net‐flux microdialysis was used to determine if changes in dialysate glutamate levels following ethanol administration are due to an increase in release or a decrease in uptake. To confirm the validity of this me... Addiction Biology journals http://www.medworm.com/rss/comments.php?id=4285150 Thu, 23 Dec 2010 00:00:00 +0100 4285150