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 'Journal of Psychopharmacology' source. Tue, 07 Feb 2012 09:35:54 +0100 http://www.medworm.com/index.php?rid=5636884&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F189%3Frss%3D1 Substance abuse and psychotic disorders have a high rate of comorbidity. Both disorders are associated with changes in the dopaminergic transmission in the mesocorticolimbic pathways of the brain. Since antipsychotic medications interact with the dopamine receptors in these pathways, these medications could affect craving for substances. In the current study, the effect of clozapine (n = 27, mean dosage 350 mg), risperidone (n = 54, mean dosage 3.46 mg) and olanzapine (n = 60, mean dosage 13.78 mg) on subjective craving for cannabis was compared in 123 patients with cannabis dependence and psychotic disorder. Patients treated with risperidone reported significantly more craving compared with patients treated with clozapine (Z = –3.19, p = .001) or olanzapine (Z = –2.24, p = .02... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636884 Fri, 27 Jan 2012 05:00:00 +0100 5636884 http://www.medworm.com/index.php?rid=5636883&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F177%3Frss%3D1 In conclusion, the available data point to the hypothesis that heavy cannabis use in adolescence could increase the risk of developing psychiatric disorders, especially in people who already have a vulnerability to develop a psychiatric syndrome. Only few papers have investigated the neurobiological substrates of this vulnerability, thus further studies are needed to clarify the molecular mechanisms underlying the effect of cannabis on the adolescent brain. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636883 Fri, 27 Jan 2012 05:00:00 +0100 5636883 http://www.medworm.com/index.php?rid=5636882&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F164%3Frss%3D1 This review focuses on the endocannabinoid system as a crucial player during critical periods of brain development, and how its disturbance either by early life stressful events or cannabis consumption may lead to important neuropsychiatric signs and symptoms. First we discuss the advantages and limitations of animal models within the framework of neuropsychiatric research and the crucial role of genetic and environmental factors for the establishment of vulnerable phenotypes. We are becoming aware of important sex differences that have emerged in relation to the psychobiology of cannabinoids. We will discuss sexual dimorphisms observed within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabi... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636882 Fri, 27 Jan 2012 05:00:00 +0100 5636882 http://www.medworm.com/index.php?rid=5636881&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F150%3Frss%3D1 Alterations in emotion regulation processes may form the basis of psychopathologies. The endocannabinoid (eCB) system, composed of endogenous ligands, the enzymatic machinery in charge of their metabolism and the specific metabotropic receptors, has emerged as a major neuromodulatory system critically involved in the control of emotional homeostasis and stress responsiveness. Data from animal models indicate that the eCB system plays a key role in brain development, and is probably involved in the control of emotional states from early developmental stages. The present review summarizes the latest information on the role of the eCB system in emotionality and anxiety-related disorders throughout the lifespan. Putative therapeutic strategies based on the pharmacological modulation of this sy... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636881 Fri, 27 Jan 2012 05:00:00 +0100 5636881 http://www.medworm.com/index.php?rid=5636880&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F144%3Frss%3D1 Cannabis use in adolescence is emerging as a risk factor for the development of psychosis. In animal studies, 9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, modulates striatal dopaminergic neurotransmission. Alterations in human striatal dopaminergic function have also been reported both in psychosis and in stimulant use. We sought to examine whether striatal dopamine D2/D3 receptor availability was altered in volunteers with a history of cannabis use using a database of previously acquired [11C]-raclopride positron emission tomography (PET) scans. Ten [11C]-raclopride scans from volunteers with a history of cannabis use were compared to ten control scans using a functional striatal subdivision region of interest (ROI) analysis. No significant differences in either o... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636880 Fri, 27 Jan 2012 05:00:00 +0100 5636880 http://www.medworm.com/index.php?rid=5636879&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F133%3Frss%3D1 The cannabinoid receptor (CNR1) and the fatty acid amide hydrolase (FAAH) genes are located on chromosomes 6 and 1 in the 6q15 and 1p33 cytogenetic bands, respectively. CNR1 encodes a seven-transmembrane domain protein of 472 amino acids, whereas FAAH encodes one transmembrane domain of 579 amino acids. Several mutations found in these genes lead to altered mRNA stability and transcription rate or a reduction of the activity of the encoded protein. Increasing evidence shows that these functional mutations are related to dependence upon cocaine, alcohol, marijuana, heroin, nicotine and other drugs. One of the most compelling associations is with the C385A single nucleotide polymorphism (SNP), which is found in the FAAH gene. For all of the genetic polymorphisms reviewed here, it is difficul... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636879 Fri, 27 Jan 2012 05:00:00 +0100 5636879 http://www.medworm.com/index.php?rid=5636878&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F125%3Frss%3D1 Rimonabant is a cannabinoid type 1 receptor (CB1) antagonist formerly used to treat obesity, but which was withdrawn from the market in late 2008 because of its association with psychiatric adverse effects such as depression and anxiety. Previously, we showed that a single dose of rimonabant produced a negative bias on an emotional word memory task, in the absence of subjective mood effects. The present study investigated whether a similar effect on emotional processing could be seen after 7 days’ daily treatment with rimonabant 20 mg, using a randomized, placebo-controlled, between-subjects design in healthy volunteers (final n = 21). In comparison with placebo, rimonabant induced a negative bias on a memory recognition task without producing a change in subjective mood. This raises... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636878 Fri, 27 Jan 2012 05:00:00 +0100 5636878 http://www.medworm.com/index.php?rid=5636877&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F114%3Frss%3D1 Animal and human studies carried out so far have established a role for the endocannabinoid system (ECS) in the regulation of energy balance. Here we critically discuss the role of the endocannabinoid signalling in brain structures, such as the hypothalamus and reward-related areas, and its interaction with neurotransmitter and neuropeptide systems involved in the regulation of food intake and body weight. The ECS has been found to interact with peripheral signals, like leptin, insulin, ghrelin and satiety hormones and the resulting effects on both central and peripheral mechanisms affecting energy balance and adiposity will be described. Furthermore, ECS dysregulation has been associated with the development of dyslipidemia, glucose intolerance and obesity; phenomena that are often accomp... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636877 Fri, 27 Jan 2012 05:00:00 +0100 5636877 http://www.medworm.com/index.php?rid=5636876&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F104%3Frss%3D1 Systemic administration of cannabidiol (CBD) attenuates cardiovascular and behavioral changes induced by re-exposure to a context that had been previously paired with footshocks. Previous results from our group using cFos immunohistochemistry suggested that the bed nucleus of the stria terminalis (BNST) is involved in this effect. The mechanisms of CBD effects are still poorly understood, but could involve 5-HT1A receptor activation. Thus, the present work investigated if CBD administration into the BNST would attenuate the expression of contextual fear conditioning and if this effect would involve the activation of 5-HT1A receptors. Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (six footshocks, 1.5 mA/3 s). Twenty-four h... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636876 Fri, 27 Jan 2012 05:00:00 +0100 5636876 http://www.medworm.com/index.php?rid=5636875&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F92%3Frss%3D1 There are two well characterized cannabinoid receptors (CBRs), CB1-Rs and CB2-Rs, with other candidates, such as GPR55, PPARs and vanilloid TRPV1 (VR1) receptors, which are either activated by cannabinoids and/or endocannabinoids (eCBs). The neuronal and functional expression of CB2-Rs in the brain has been much less well characterized in comparison with the expression of the ubiquitous CB1-Rs. CB2-Rs were previously thought to be predominantly expressed in immune cells in the periphery and were traditionally referred to as peripheral CB2-Rs. We and others have now demonstrated the expression of CB2-Rs in neuronal, glial and endothelial cells in the brain, and this warrants a re-evaluation of the CNS effects of CB2-Rs. In the present review we summarize our current understanding of CNR2 ge... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636875 Fri, 27 Jan 2012 05:00:00 +0100 5636875 http://www.medworm.com/index.php?rid=5636874&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F83%3Frss%3D1 The endocannabinoid system regulates nociception and aversion and mediates fear-conditioned analgesia (FCA). We investigated the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which inhibits the catabolism of the endocannabinoid anandamide and related N-acylethanolamines, on expression of FCA and fear and pain related behaviour per se in rats. We also examined associated alterations in the expression of the signal transduction molecule phospho-Akt in the periaqueductal grey (PAG) by immunoblotting. FCA was modelled by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. URB597 (0.3 mg/kg, i.p.) enhanced FCA and increased fear-related behaviour in formalin-treated rats. Conditioned fear per se in non-formalin-treated rats was asso... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636874 Fri, 27 Jan 2012 05:00:00 +0100 5636874 http://www.medworm.com/index.php?rid=5636873&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F71%3Frss%3D1 Stress activates the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS), resulting in cardiovascular responses. The endocannabinoid system (ECS), a ubiquitously expressed lipid signalling system, modulates both HPA and SNS activity. The purpose of this review is to explore the possible involvement/role of the ECS in the cardiovascular response to stress. The ECS has numerous cardiovascular effects including modulation of blood pressure, heart rate, the baroreflex, and direct vascular actions. It is also involved in a protective manner in response to stressors in cardiac preconditioning, and various stressors (for example, pain, orthostasis and social stress) increase plasma levels of endocannabinoids. Given the multitude of vascular effects of endoca... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636873 Fri, 27 Jan 2012 05:00:00 +0100 5636873 http://www.medworm.com/index.php?rid=5636872&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F56%3Frss%3D1 Exposure to behavioural stress normally triggers a complex, multilevel response of the hypothalamic–pituitary–adrenal (HPA) axis that helps maintain homeostatic balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic stress, few studies have directly addressed its response to acute stress. Here we show that acute restraint stress enhances eCB-dependent modulation of GABA release measured by whole-cell voltage clamp of inhibitory postsynaptic currents (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro. Both Ca2+-dependent, eCB-mediated depolarization-induced suppression of inhibition (DSI), and muscarinic cholinergic receptor (mAChR)-mediated eCB mobilization are enhanced following acute stress exposure. DSI enhancement is dependent on the activatio... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636872 Fri, 27 Jan 2012 05:00:00 +0100 5636872 http://www.medworm.com/index.php?rid=5636871&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F40%3Frss%3D1 Administration of Cannabis sativa derivatives causes anxiolytic or anxiogenic effects in humans and laboratory animals, depending on the specific compound and dosage used. In agreement with these findings, several studies in the last decade have indicated that the endocannabinoid system modulates neuronal activity in areas involved in defensive responses. The mechanisms of these effects, however, are still not clear. The present review summarizes recent data suggesting that they involve modulation of glutamate and GABA-mediated neurotransmission in brain sites such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of the stria terminalis, hippocampus and dorsal periaqueductal gray. Moreover, we also discuss results indicating that, in these regions, the endocannabinoid syste... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636871 Fri, 27 Jan 2012 05:00:00 +0100 5636871 http://www.medworm.com/index.php?rid=5636870&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F23%3Frss%3D1 Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations. This dual functionality, together with the plasticity of CB1 receptor expression, particularly on GABAergic neurons, as induced by stressful and rewarding experiences, gives the ECS a unique regulatory capacity for maintaining emotional homeostasis. However, the promi... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636870 Fri, 27 Jan 2012 05:00:00 +0100 5636870 http://www.medworm.com/index.php?rid=5636869&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F1%2F7%3Frss%3D1 The study of endocannabinoid pharmacology has proceeded from the discovery of 9-tetrahydrocannabinol, the main psychoactive compound in Cannabis sativa, to the identification of an endogenous endocannabinoid system that is essential for physiological modulation of neuronal functions. We have not yet achieved a complete understanding of the various roles of the endocannabinoids, but this is one of the fastest-growing fields in psychopharmacology. This review starts with a brief historical description of the discovery of the endocannabinoids and then focuses on recent pharmacological advances and recently discovered endocannabinoid mechanisms of action (e.g. functional selectivity, allosterism, and receptor trafficking). Finally, we will discuss the contention that the existence of evidence-... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636869 Fri, 27 Jan 2012 05:00:00 +0100 5636869 http://www.medworm.com/index.php?rid=5636868&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F26%2F1%2F3%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636868 Fri, 27 Jan 2012 05:00:00 +0100 5636868 http://www.medworm.com/index.php?rid=5636867&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F324%3Frss%3D1 Hyperprolactinaemia in antipsychotic treated patients with schizophrenia is a consequence of D2 receptor (DRD2) blockade. Alcohol use disorder is commonly comorbid with schizophrenia and low availability of striatal DRD2 may predispose individuals to alcohol use. In this pilot study we investigated whether hyperprolactinaemia secondary to pharmacological DRD2 blockade was associated with alcohol use disorder in 219 (178 males and 41 females) patients with schizophrenia. Serum prolactin determinations were made in patients diagnosed with schizophrenia and maintained on antipsychotic agents. Clinical assessment included demographics, family history and administration of the AUDIT (Alcohol Use Disorders Identification Test). Higher AUDIT scores were associated with prolactin-raising antipsych... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636867 Fri, 27 Jan 2012 05:00:00 +0100 5636867 http://www.medworm.com/index.php?rid=5636866&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F315%3Frss%3D1 Nicotinic acetylcholine receptors mediate some of the rewarding and motivational effects of ethanol, including relapses. Relapses are common in drug addicts during abstinence when exposure to any stressor ensues. However, the role of nicotinic acetylcholine receptors in the ethanol- and stress-induced reinstatement of ethanol-induced conditioned place preference has not yet been explored. Therefore, the present study investigated the influence of mecamylamine, a nicotinic acetylcholine receptors antagonist on acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in adult male Swiss mice. The results revealed that mecamylamine (0.1–10 µg/mouse, intracerebroventricularly) dose dependently prevented the development, expression, and reinstatemen... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636866 Fri, 27 Jan 2012 05:00:00 +0100 5636866 http://www.medworm.com/index.php?rid=5636865&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F303%3Frss%3D1 In conclusion, GSK598809 causes elevation of serum prolactin and a small decrease in adaptive tracking performance. After co-administration with alcohol, effects of GSK598809 are mainly additive and the combination is well tolerated in healthy volunteers. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636865 Fri, 27 Jan 2012 05:00:00 +0100 5636865 http://www.medworm.com/index.php?rid=5636864&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F292%3Frss%3D1 Essential tremor (ET) is a common movement disorder. Animal studies show that histaminergic modulation may affect the pathological processes involved in the generation of ET. Histamine-3 receptor inverse agonists (H3RIA) have demonstrated attenuating effects on ET in the harmaline rat model. In this double-blind, three-way cross-over, single-dose, double-dummy study the effects of 25 mg of a novel H3RIA (MK-0249) and a stable alcohol level (0.6 g L–1) were compared with placebo, in 18 patients with ET. Tremor was evaluated using laboratory tremorography, portable tremorography and a clinical rating scale. The Leeds Sleep Evaluation Questionnaire (LSEQ) and a choice reaction time (CRT) test were performed to evaluate potential effects on sleep and attention, respectively. A steady sta... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636864 Fri, 27 Jan 2012 05:00:00 +0100 5636864 http://www.medworm.com/index.php?rid=5636863&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F282%3Frss%3D1 This study showed that alcohol reduced maximum tremor power, as assessed by laboratory accelerometry, unlike TPA023, which decreased tremor symptoms to some extent but not significantly. This study showed that treatment with an α2,3 subunit-selective GABAA partial agonist was less effective than a stable level of alcohol in reducing ET symptoms. These results provide no support for a therapeutic role of TPA023 in the suppression of ET symptoms. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636863 Fri, 27 Jan 2012 05:00:00 +0100 5636863 http://www.medworm.com/index.php?rid=5636862&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F273%3Frss%3D1 We report [11C]Ro15 4513 brain uptake for 8 alcohol-dependent men and 11 healthy controls. We found a significant reduction in [11C]Ro15 4513 binding in the nucleus accumbens, parahippocampal gyri, right hippocampus and amygdala in the alcohol-dependent compared with the healthy control group. Levels of [11C]Ro15 4513 binding in both hippocampi were significantly and positively associated with performance on a delayed verbal memory task in the alcohol-dependent but not the control group. We speculate that the reduced limbic [11C]Ro15 4513 binding seen here results from the effects of alcohol, though we cannot currently distinguish whether they are compensatory in nature or evidence of brain toxicity. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636862 Fri, 27 Jan 2012 05:00:00 +0100 5636862 http://www.medworm.com/index.php?rid=5636861&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F262%3Frss%3D1 This study examined alcohol effects at the ‘automated’ level of processing essential to many complex visual processing tasks (e.g., reading, visual search) that involve ongoing modifications or reprogramming of well-practiced routines. Data from 30 participants (16 male) were collected in two counterbalanced sessions (alcohol vs. no-alcohol control; mean breath alcohol concentration = 68 mg/dL vs. 0 mg/dL). Eye movements were recorded during a double-step task where 75% of trials involved two target stimuli in rapid succession (inter-stimulus interval [ISI] = 40, 70, or 100 ms) so that they could elicit two distinct saccades or eye movements (double steps). On 25% of trials a single target appeared. Results indicated that saccade latencies were longer under alcohol. In addition... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636861 Fri, 27 Jan 2012 05:00:00 +0100 5636861 http://www.medworm.com/index.php?rid=5636860&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F254%3Frss%3D1 Alcohol consumption is associated with increases in aggressive behaviour, but the mechanisms underlying this relationship are poorly understood. One mechanism by which alcohol consumption may influence behaviour is via alterations in the processing of social cues such as gaze. We investigated the effects of acute alcohol consumption on the perception of gaze, using a task in which participants determined whether a stimulus face was looking towards or away from them. Gaze direction varied across trials, allowing calculation of a threshold at which participants considered gaze to switch from direct to averted. Target faces varied in both sex and attractiveness. Thirty social drinkers attended three randomized experimental sessions. At each session, participants consumed 0.0, 0.2 or 0.4 g/kg ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636860 Fri, 27 Jan 2012 05:00:00 +0100 5636860 http://www.medworm.com/index.php?rid=5636859&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F245%3Frss%3D1 We investigated (1) the effects of alcohol on cognitive biases for alcohol-related cues, (2) the effects of drinking status on alcohol-related cognitive biases and (3) the similarity of any effects of alcohol across two measures of alcohol cognitive bias. Healthy, heavy and light social alcohol users (n = 72) were examined in a single-blind placebo-controlled design. Participants received 0.00 g/kg, 0.13 g/kg or 0.40 g/kg of alcohol in a between-subjects design and then completed both a modified Stroop task and a visual probe task. Modified Stroop data indicated a main effect of cue type, which was qualified by drinking status, with heavier drinkers slower to respond to alcohol-related cues. Visual probe data, in contrast, indicated a significant interaction effect between validity (valid:... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636859 Fri, 27 Jan 2012 05:00:00 +0100 5636859 http://www.medworm.com/index.php?rid=5636858&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F232%3Frss%3D1 Problematic alcohol use and stress response dampening (SRD) are intimately interconnected. Recent evidence suggests that alcohol produces selective SRD during uncertain but not certain threat. We systematically varied shock probability in a novel task assessing alcohol SRD during low probable/uncertain threat, while holding temporal precision of threat constant. Intoxicated (0.08% target blood alcohol concentration) and placebo participants completed a cued shock threat task in which probability of shock administration at the offset of brief visual cues varied parametrically. High probability (100%) shock cues represented certain threat as used in earlier research, while lower probability (20% and 60%) shock cues provided novel uncertain threat conditions. Startle potentiation during cues ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636858 Fri, 27 Jan 2012 05:00:00 +0100 5636858 http://www.medworm.com/index.php?rid=5636857&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F221%3Frss%3D1 The stress-dampening effects of alcohol have been attributed to ‘appraisal disruption’– decreased ability of stimuli to evoke threatening associations in memory. Appraisal disruption could apply to oneself as well as situational stimuli. This question was investigated in undergraduate drinkers (n = 90/Gender) with low or high anxiety sensitivity (AS; n = 90/AS Group), a trait linked with hyper-vigilance to threat. Subjects received alcohol (0.7 g/kg males; 0.63 g/kg females), placebo or soft drink and performed a speech about their appearance. Sequence of drink administration and speech advisory (threat) was manipulated between subjects: Threat before Drink, Threat after Drink, No-Threat Control. The Implicit Association Test measured self-relevant associations based upon... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636857 Fri, 27 Jan 2012 05:00:00 +0100 5636857 http://www.medworm.com/index.php?rid=5636856&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F213%3Frss%3D1 In this paper we discuss the relative physical, psychological and social harms of the two most frequently used intoxicant drugs in the UK, namely cannabis and alcohol. Over the past 40 years, the use of both drugs has risen significantly with differential consequences. It is argued that increased policing of cannabis use under the current drug classification system will lead to increased criminalization of young people, but is unlikely to significantly reduce the rates of schizophrenia and psychosis. In comparison, increases in alcohol drinking are related to significant increases in liver cirrhosis hospital admissions and mortality, at a time when mortality rates from other major causes are on the decline. A recent expert-led comparison of the health and social harms to the user and to ot... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636856 Fri, 27 Jan 2012 05:00:00 +0100 5636856 http://www.medworm.com/index.php?rid=5636855&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F26%2F2%2F205%3Frss%3D1 A number of compounds already in use as medications for various indications substitute for ethanol at clinically relevant brain pathways, in particular, at gamma-aminobutyric acid (GABA) receptors. Nevertheless, although substitute medications have been recognized for heroin and tobacco dependence, patients with alcohol dependence are rarely offered an analogous approach. Benzodiazepines may have paradoxical effects, and abuse and dependence are known. Baclofen (GABAB agonist) has not been associated with dependence or misuse and has been effective in several trials in preventing relapse, although research is required to establish the optimal dosing regimen. GABA-ergic anticonvulsants, helpful in treating withdrawal, have yet to emerge as effective in relapse prevention. Clomethiazole and ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636855 Fri, 27 Jan 2012 05:00:00 +0100 5636855 http://www.medworm.com/index.php?rid=5636854&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F26%2F2%2F199%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5636854 Fri, 27 Jan 2012 05:00:00 +0100 5636854 http://www.medworm.com/index.php?rid=5579228&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F12%2F1732%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579228 Tue, 10 Jan 2012 05:00:00 +0100 5579228 http://www.medworm.com/index.php?rid=5579227&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F12%2F1730%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579227 Tue, 10 Jan 2012 05:00:00 +0100 5579227 http://www.medworm.com/index.php?rid=5579226&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1720%3Frss%3D1 Reduced glutamatergic signaling may contribute to cognitive dysfunction in schizophrenia. Glutamatergic synapses might be the site of primary abnormalities in this disorder with the dopaminergic changes being secondary to altered glutamatergic transmission. Isolation rearing of rats from weaning has been used as an experimental model for affective disorders like schizophrenia. In this immunohistochemistry study we evaluate the changes in the expression of GluR1 and GluR2 AMPA receptors in the hippocampus, amygdala and entorhinal cortex induced by isolation rearing. Two groups of Wistar rats (grouped and isolated, n = 6/each) were used. Isolation rearing induced a significant decrease in GluR1- and GluR2-immunopositive cells in the hippocampus. For GluR1 the reduction was 31% in the hilus o... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579226 Tue, 10 Jan 2012 05:00:00 +0100 5579226 http://www.medworm.com/index.php?rid=5579225&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1712%3Frss%3D1 Obsessive–compulsive disorder (OCD) is a chronic and disabling psychiatric disease with a lifetime prevalence of 2–3%. People with OCD suffer from intrusive, unwanted and recurrent thoughts (obsessions) and/or repetitive ritualistic behaviors (compulsions). The aim of this study is to quantify the dimensions of ritualistic ‘compulsive-like’ behavior in quinpirole-induced behavior in rats by using T-pattern behavioral analysis. In addition, we investigated whether the behavioral effects elicited by quinpirole sensitization remained after 2 weeks of cessation of treatment. Finally, to study the neurobiological underpinnings of this ‘compulsive-like’ behavior, we investigated the effect of quinpirole treatment on the extracellular dopamine levels in the nuc... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579225 Tue, 10 Jan 2012 05:00:00 +0100 5579225 http://www.medworm.com/index.php?rid=5579224&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1703%3Frss%3D1 Lamotrigine is suggested to have potential as an add-on treatment for patients with schizophrenia. Supporting evidence comes from the efficacy of the drug in models of psychotic-like behaviour induced by N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP). These drugs enhance levels of the monoamines in the cortex, which may contribute to their psychotomimetic effects. The ability of lamotrigine to prevent these neurochemical changes has not been examined. We studied PCP-evoked overflow of noradrenaline, dopamine and serotonin in the medial prefrontal cortex of awake rats using microdialysis. Rats were administered lamotrigine or vehicle, followed by PCP. Locomotor activity was also recorded before and after drug treatment. Lamotrigine did not have an influence on... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579224 Tue, 10 Jan 2012 05:00:00 +0100 5579224 http://www.medworm.com/index.php?rid=5579223&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1691%3Frss%3D1 Fas-associated death domain (FADD) phosphorylation was recently implicated in opiate-induced neuroplasticity. To further explore the role of FADD in the mechanisms of morphine-induced physical dependence, the regulation of cortical p-FADD (and their interactions with α2-adrenoceptors and other signalling pathways) was assessed during spontaneous opiate withdrawal (SW) in morphine-dependent rats (10–100 mg/kg for 6 days). The main results indicated that oligomeric p-FADD in the cerebral cortex mirrored the time course of morphine SW (12–96 h), which resulted in a striking correlation between p-FADD and the intensity (behavioural scores) of morphine abstinence (Spearman correlation coefficient: 0.59, n = 39, p < 0.0001). The inactivation of brain α2-adrenoceptors (... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579223 Tue, 10 Jan 2012 05:00:00 +0100 5579223 http://www.medworm.com/index.php?rid=5579222&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1676%3Frss%3D1 We have analysed the long-term effects of adolescent (postnatal day 28–43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB1 cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was on... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579222 Tue, 10 Jan 2012 05:00:00 +0100 5579222 http://www.medworm.com/index.php?rid=5579221&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1661%3Frss%3D1 Brain -aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT)2C receptors are implicated in the neuronal regulation of reward- and aversion-related behaviour. Within the mesocorticolimbic pathways of the brain, relationships between GABA containing neurons and 5-HT2C receptor activity may be important in this context. The primary aim of this study was to investigate the role of NAc shell GABA receptors on ventral tegmental area intracranial self-stimulation (ICSS) and to examine the systemic effects of GABAergic ligands in this context. The second aim was to investigate the relationship between GABA receptor- and 5-HT2C receptor-related ICSS behaviour, using systemic administration of the selective agonist WAY 161503. Locomotor activity was assessed to compare the potential motor effects ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579221 Tue, 10 Jan 2012 05:00:00 +0100 5579221 http://www.medworm.com/index.php?rid=5579220&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1649%3Frss%3D1 Latent inhibition (LI) is demonstrated when non-reinforced pre-exposure to a to-be-conditioned stimulus retards later learning. Learning is similarly retarded in overshadowing, in this case using the relative intensity of competing cues to manipulate associability. Electrolytic/excitotoxic lesions to shell accumbens (NAc) and systemic amphetamine both reliably abolish LI. Here a conditioned emotional response procedure was used to demonstrate LI and overshadowing and to examine the role of dopamine (DA) within NAc. Experiment 1 showed that LI but not overshadowing was abolished by systemic amphetamine (1.0 mg/kg i.p.). In Experiment 2, 6-hydroxydopamine (6-OHDA) was used to lesion DA terminals within NAc: both shell- and core- (plus shell-)lesioned rats showed normal LI and overshadowing. ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579220 Tue, 10 Jan 2012 05:00:00 +0100 5579220 http://www.medworm.com/index.php?rid=5579219&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1639%3Frss%3D1 Systemic injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (LNO) prevents the disruptive effect of amphetamine (Amph) on prepulse inhibition (PPI), a sensorimotor gating model in which the amplitude of the acoustic startle response (ASR) to a startling sound (pulse) is reduced when preceded immediately by a weaker stimulus (prepulse). Given that dopamine (DA) projections to the basolateral amygdala (BLA) are involved in the control of information processing, our aim was to investigate if intra-BLA administration of LNO would modify the disruption caused by the DA agonists, Amph, apomorphine (Apo) and quinpirole (QNP), on PPI. Male Wistar rats received bilateral intra-BLA microinjections (0.2 µL/min/side) of combined treatments (saline or LNO 11 µg follow... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579219 Tue, 10 Jan 2012 05:00:00 +0100 5579219 http://www.medworm.com/index.php?rid=5579218&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1632%3Frss%3D1 This study examined the acute effects of modulating the glycine site of the NMDA receptor (with high-dose glycine) on sensory gating as measured by PPI. Sixteen healthy male subjects (final sample size of 12) participated in a double-blind, placebo-controlled, crossover design in which each subject was tested under two acute treatment conditions separated by at least a 5-day washout period; placebo and 0.8 g/kg glycine. PPI was recorded 45 min post treatment using electromyography of the eye-blink response. Relative to placebo, high-dose glycine significantly impaired sensorimotor gating as demonstrated by a decrease in PPI (t(11) = –2.983, p < 0.05). Administration of a high dose of glycine is associated with impairments in PPI supporting earlier observations in animals and patie... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579218 Tue, 10 Jan 2012 05:00:00 +0100 5579218 http://www.medworm.com/index.php?rid=5579217&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1623%3Frss%3D1 In this study, we gave 0.45 mg/kg dexamphetamine to healthy volunteers (final n = 18) using both auditory and visual three-stimulus P3 procedures. Dexamphetamine significantly reduced P3 amplitudes to auditory target, rare non-target and standard stimulus amplitudes. The reduction in auditory P3 induced by dexamphetamine was proportional across stimulus types to placebo P3 values. There were no effects of dexamphetamine on visual P3. We demonstrate a reduced auditory P3 similar to that seen in schizophrenia and other psychotic illnesses. This possibly reflects a common pathology which is hypothesized within the P3 literature to be related to attention and working memory. Differences between auditory and visual P3 modulation may be related to regional variations in catecholamine or specific... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579217 Tue, 10 Jan 2012 05:00:00 +0100 5579217 http://www.medworm.com/index.php?rid=5579216&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1614%3Frss%3D1 We examined the effects of estrogen pre-treatment on modulation of loudness dependence of the auditory evoked potential (LDAEP) and mismatch negativity by the 5-HT1A receptor partial agonist, buspirone. Using a double-blind, placebo-controlled, repeated-measures design in healthy female volunteers, we observed that buspirone treatment significantly increased LDAEP slope. Estrogen increased LDAEP slope on its own, and a further LDAEP increase by buspirone was not seen after estrogen pre-treatment. Similar results were observed for mismatch negativity, where buspirone caused a small increase of latency, although not amplitude, after placebo but not estrogen pre-treatment, which enhanced mismatch negativity latency on its own. These results are in line with our previous findings on prepulse i... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579216 Tue, 10 Jan 2012 05:00:00 +0100 5579216 http://www.medworm.com/index.php?rid=5579215&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1600%3Frss%3D1 Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders. There is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Some recent studies have investigated the effects of antipsychotic medications on gating in healthy volunteers exhibiting low levels of gating, rather than in patients. Therefore, the current study investigated the influence of sertindole versus placebo in two separate experimental sessions, on PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and high baseline gating levels. Sertindole increased PPI and P50 suppression in healthy su... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579215 Tue, 10 Jan 2012 05:00:00 +0100 5579215 http://www.medworm.com/index.php?rid=5579214&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F12%2F1581%3Frss%3D1 Pharmacological treatments have been widely investigated in pre-clinical animal trials to evaluate their usefulness in reducing cognitive, behavioural and motor problems after traumatic brain injury (TBI). However, the relative efficacy of these agents has yet to be evaluated, making it difficult to assess the strength of evidence for their use in a clinical population. A meta-analytic review of research (1980–2009) was therefore conducted to examine the impact of pharmacological treatments administered to adult male rodents after experimental TBI on cognitive, behavioural, and motor outcome. The PubMed and PsycInfo databases were searched using 35 terms. Weighted Cohen’s d effect sizes, percent overlap, Fail-Safe N statistics and confidence intervals were calculated for each t... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5579214 Tue, 10 Jan 2012 05:00:00 +0100 5579214 http://www.medworm.com/index.php?rid=5502688&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1573%3Frss%3D1 Studies of the chronic effects of MDMA, or ‘ecstasy’, in humans have been largely inconsistent. We explored whether study-level characteristics are associated with the effect size estimate reported. We based our analyses on the recent systematic review by Rogers and colleagues, focusing on those meta-analyses within this report where there was a relatively large number of studies contributing to each individual meta-analysis. Linear regression was used to investigate the association between study level variables and effect size estimate, weighted by the inverse of the SE of the effect size estimate, with cluster correction for studies which contributed multiple estimates. This indicated an association between effect size estimate and both user group, with smaller estimates amon... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502688 Mon, 12 Dec 2011 05:00:00 +0100 5502688 http://www.medworm.com/index.php?rid=5502687&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1568%3Frss%3D1 The objective of this paper is to describe three cases of combat-related posttraumatic stress disorder (PTSD), largely refractory to standard medication treatment who responded well to psychostimulant treatment. Symptoms of PTSD potentially result from chronic, stress-induced dopaminergic dysfunction in the prefrontal cortex/basal ganglia system. Psychostimulants, by their relative propensity to enhance dopamine (DA) activity within these brain regions, may have particular value in targeting this dysfunction. Evidence of dopaminergic dysfunction following chronic stress is reviewed and possible mechanism of action of psychostimulants is explored. Psychostimulants appeared to be well tolerated and beneficial in the treatment of the cases of combat-related PTSD reported. General applicabilit... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502687 Mon, 12 Dec 2011 05:00:00 +0100 5502687 http://www.medworm.com/index.php?rid=5502686&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1562%3Frss%3D1 This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502686 Mon, 12 Dec 2011 05:00:00 +0100 5502686 http://www.medworm.com/index.php?rid=5502685&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1548%3Frss%3D1 Psilocin (4-hydroxy-N,N-dimethyltryptamine) is a hallucinogen that acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors. Psilocin is the active metabolite of psilocybin, a hallucinogen that is currently being investigated clinically as a potential therapeutic agent. In the present investigation, we used a combination of genetic and pharmacological approaches to identify the serotonin (5-HT) receptor subtypes responsible for mediating the effects of psilocin on head twitch response (HTR) and the behavioral pattern monitor (BPM) in C57BL/6J mice. We also compared the effects of psilocin with those of the putative 5-HT2C receptor-selective agonist 1-methylpsilocin and the hallucinogen and non-selective serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Psilocin, 1-... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502685 Mon, 12 Dec 2011 05:00:00 +0100 5502685 http://www.medworm.com/index.php?rid=5502684&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1543%3Frss%3D1 Recently, several reports have indicated instability of the ecstasy market in the Netherlands and other EU countries. In the current study, we demonstrate this instability in the Netherlands, showing a decrease of ecstasy tablets containing 3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in 2009. In addition, we describe a partial replacement of MDMA in tablets sold as ecstasy by a previously unseen substance, mephedrone (or 4-methylmethcathinone). Mephedrone was quantified and ecstasy tablets contained between 96 and 155 mg of this new compound. So far, no studies about mephedrone’s effects have been published. For this study, we gathered information on the acute subjective effects of mephedrone from 70 regular ecstasy users. Overall, the majority of users considered the ef... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502684 Mon, 12 Dec 2011 05:00:00 +0100 5502684 http://www.medworm.com/index.php?rid=5502683&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1533%3Frss%3D1 Clinical characteristics and risk factors associated with sudden unexplained death (SUD) in the psychiatric population are unclear. Psychiatric in-patients (England, Wales) who met criteria for SUD were identified (1 March 1999–31 December 2005). Cases were matched with controls (in-patients alive on the day a SUD occurred). Data were collected via questionnaires. Some 283 cases of SUD were identified (41 annually), with a rate of 2.33/10,000 mental health admissions (in England). Electrocardiograms were not routine, cardiopulmonary resuscitation equipment was sometimes unavailable, attempts to resuscitate patients were carried out on one-half of all patients and post mortems/inquiries were not routine. Restraint and seclusion were uncommon. Risk factors included: benzodiazepines (od... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502683 Mon, 12 Dec 2011 05:00:00 +0100 5502683 http://www.medworm.com/index.php?rid=5502682&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1524%3Frss%3D1 The aim of the study was to investigate predictors of offending among prisoners from official records after controlling for age at first conviction and antisocial personality disorder. The participants were 198 Scottish prisoners, who had completed Diagnostic Statistical Manual IV screens for child and adult attention-deficit hyperactivity disorder (ADHD) symptoms and the Millon Clinical Multiaxial Inventory III for Axis I and Axis II disorders. The ADHD symptomatic group had significantly higher rates of total, acquisitive and violent offending than other prisoners, as well as greater regular heroin use. Hierarchical multiple regressions, using child and adult symptoms as dimensions, showed that frequent use of heroin in the year prior to imprisonment was the single most powerful predicto... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502682 Mon, 12 Dec 2011 05:00:00 +0100 5502682 http://www.medworm.com/index.php?rid=5502681&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1517%3Frss%3D1 This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two particpants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after sing... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502681 Mon, 12 Dec 2011 05:00:00 +0100 5502681 http://www.medworm.com/index.php?rid=5502680&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1508%3Frss%3D1 The cholinergic system is involved in the modulation of both bottom-up and top-down attentional control. Top-down attention engages multiple executive control processes, but few studies have investigated whether all or selective elements of executive functions are modulated by the cholinergic system. To investigate the acute effects of the pro-cholinergic donepezil in young, healthy volunteers on distinct components of executive functions we conducted a double-blind, placebo-controlled, independent-groups design study including 42 young healthy male participants who were randomly assigned to one of three oral treatments: glucose (placebo), donepezil 5 mg or donepezil 7.5 mg. The test battery included measures of different executive components (shifting, updating, inhibition, dual-task perf... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502680 Mon, 12 Dec 2011 05:00:00 +0100 5502680 http://www.medworm.com/index.php?rid=5502679&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1496%3Frss%3D1 Salvia divinorum is a hallucinogenic plant with ethnopharmacological and recreational uses. It differs from classic serotonergic hallucinogens such as LSD and psilocin in both phenomenology and potent agonist activity of the active component salvinorin A at -opioid receptors. Awareness of S. divinorum has grown recently, with both an increase in its public representation and concern over its potential harmful effects. This discussion is particularly relevant as S. divinorum is legal to use in many countries and regions and easily available through online retailers. Drawing upon previous investigations of S. divinorum and other hallucinogens, this study surveyed 154 recent users and questioned them on their use behaviours, consequences of use and other attitudinal measures. Although reporti... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502679 Mon, 12 Dec 2011 05:00:00 +0100 5502679 http://www.medworm.com/index.php?rid=5502678&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1485%3Frss%3D1 Nicotine enhances attentional functions. Since chronic nicotine exposure through smoking induces neuroadaptive changes in the brain at a structural and molecular level, the present functional MRI (fMRI) study aimed at investigating the neural mechanisms underlying visuospatial and sustained attention in smokers and non-smokers. Visuospatial attention was assessed with a location-cueing paradigm, while sustained attention was measured by changes in response speed over time. During invalid trials, neural activity within the basal forebrain was selectively enhanced in smokers and higher basal forebrain activity was associated with increased parietal cortex activation. Moreover, higher levels of expired carbon monoxide in smokers before scanning were associated with higher parietal cortex acti... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502678 Mon, 12 Dec 2011 05:00:00 +0100 5502678 http://www.medworm.com/index.php?rid=5502677&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1480%3Frss%3D1 In conclusion, our results show a positive association between BDNF serum levels and opiate craving in opiate-dependent patients. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502677 Mon, 12 Dec 2011 05:00:00 +0100 5502677 http://www.medworm.com/index.php?rid=5502676&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1469%3Frss%3D1 Aripiprazole is a dopamine D2 receptor partial agonist undergoing evaluation as a pharmacotherapy for stimulant-use disorders. Acutely administered aripiprazole attenuates the discriminative stimulus and other behavioral effects of d-amphetamine in humans; however, whether aripiprazole attenuates the effects of more commonly abused stimulants is unknown. The aim of this experiment was to assess the discriminative stimulus, subject-rated and cardiovascular effects of oral cocaine alone and following acute administration of aripiprazole in humans. Eight cocaine-dependent subjects learned to discriminate 150 mg cocaine from placebo. After acquiring the discrimination, the effects of cocaine (0, 25, 50, 100 and 200 mg) administered alone and in combination with aripiprazole (15 mg) were determ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502676 Mon, 12 Dec 2011 05:00:00 +0100 5502676 http://www.medworm.com/index.php?rid=5502675&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1462%3Frss%3D1 In this study we tested whether IV THC led to an increase in striatal DA release compared to placebo. We also investigated whether DA release and positive psychotic symptoms were related. Eleven healthy male volunteers completed two 123I-iodobenzamide ([123I]IBZM) single photon emission tomography (SPET) sessions and received IV THC (2.5 mg) or placebo in a randomized counterbalanced order, under double-blind conditions. Analysable data were obtained from nine participants. The Positive and Negative Syndrome Scale (PANSS) was used to rate psychotomimetic effects. Striatal binding index values were calculated using the occipital cortex as a reference region. Both the PANSS positive and general symptoms increased significantly at 30 min following IV THC. There were no significant differences... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502675 Mon, 12 Dec 2011 05:00:00 +0100 5502675 http://www.medworm.com/index.php?rid=5502674&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1453%3Frss%3D1 A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality – Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in a... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502674 Mon, 12 Dec 2011 05:00:00 +0100 5502674 http://www.medworm.com/index.php?rid=5502673&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1434%3Frss%3D1 Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1–4 oral doses of psilocybin (45–315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adv... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502673 Mon, 12 Dec 2011 05:00:00 +0100 5502673 http://www.medworm.com/index.php?rid=5502672&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F11%2F1415%3Frss%3D1 The opioid system plays a crucial role in the neural modulation of anxiety. The involvement of opioid ligands and receptors in physiological and dysfunctional forms of anxiety is supported by findings from a wide range of preclinical and clinical studies, including clinical trials, experimental research, and neuroimaging, genetic, and epidemiological data. In this review we provide a summary of studies from a variety of research disciplines to elucidate the role of the opioid system in the neurobiology of anxiety. First, we report data from preclinical studies using animal models to examine the modulatory role of central opioid system on defensive responses conducive to fear and anxiety. Second, we summarize the human literature providing evidence that clinical and experimental human studi... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5502672 Mon, 12 Dec 2011 05:00:00 +0100 5502672 http://www.medworm.com/index.php?rid=5466960&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1399%3Frss%3D1 Huntington’s disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466960 Thu, 01 Dec 2011 05:00:00 +0100 5466960 http://www.medworm.com/index.php?rid=5466959&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1388%3Frss%3D1 Chronic mild stress (CMS)-induced ‘anhedonia’ is a predictive model of antidepressant activity. We assessed the reversal of CMS-induced behavioral changes by asenapine, the antidepressant imipramine, and the atypical antipsychotics olanzapine and risperidone. Secondarily, the ability of these agents to facilitate intracranial self-stimulation (ICSS) was assessed to ensure that any attenuation of CMS-induced anhedonia was not associated with an overt hedonic profile. After 2 weeks of CMS, male Wistar rats were administered asenapine (0.06–0.6 mg/kg), olanzapine (2 mg/kg), risperidone (0.5 mg/kg), or imipramine (10 mg/kg) by intraperitoneal injection over 5 weeks to examine their ability to reverse CMS-induced reductions in the intake of a sucrose solution. For the ICSS stu... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466959 Thu, 01 Dec 2011 05:00:00 +0100 5466959 http://www.medworm.com/index.php?rid=5466958&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1378%3Frss%3D1 A major hypothesis of depression postulates that a dysregulation of the neurotrophin systems is directly involved in the pathophysiology of depression, and that restoration of such deficits may underlie the therapeutic efficacy of antidepressant treatment. One key finding supporting this hypothesis is upregulation of brain derived neurotrophic factor (BDNF) in the hippocampus after antidepressant treatment. Here, we further test the hypothesis of BDNF involvement in antidepressant action in a genetic rat model of depression after chronic oral treatment with escitalopram, nortriptyline or placebo. Active treatments had significant behavioural antidepressant-like actions in female rats of the Flinders Sensitive Line (FSL) and non-selected Sprague Dawley (SD) rats, while Flinders Resistant Li... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466958 Thu, 01 Dec 2011 05:00:00 +0100 5466958 http://www.medworm.com/index.php?rid=5466957&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1365%3Frss%3D1 In conclusion, while the antidepressant-like effects of estrogens depended on the time at which treatment is initiated after OVX as well as on the estrogenic compound used, antidepressant-like effects of FLX and DMI were not blocked by OVX. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466957 Thu, 01 Dec 2011 05:00:00 +0100 5466957 http://www.medworm.com/index.php?rid=5466956&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1357%3Frss%3D1 There is a need for antidepressants with novel mechanisms of action. One approach has been to develop compounds that inhibit reuptake of all three monoamines in the central nervous system, for example DOV216,303. Differential reinforcement of low-rate (72-s) responding is a behavioral test that is predictive of antidepressant-like properties. The effects of antidepressant compounds belonging to multiple classes, the anxiolytic diazepam and the antipsychotic haloperidol, were assessed in the DRL-72s task. Subsequently, the antidepressant-like properties of acute DOV216,303 were assessed. The selective serotonin reuptake inhibitor fluvoxamine, the preferential norepinephrine reuptake inhibitor desipramine and the tricyclic antidepressant imipramine exhibited antidepressant-like properties in... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466956 Thu, 01 Dec 2011 05:00:00 +0100 5466956 http://www.medworm.com/index.php?rid=5466955&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1347%3Frss%3D1 Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Accordingly, nicotine enhances antidepressant-like actions of reuptake inhibitors selective for serotonin or noradrenaline in the mouse forced swim test and the mouse tail suspension test. Both high-affinity α4β2 and low-affinity α7 nicotinic acetylcholine receptor subtypes are implicated in nicotine-mediated release of serotonin and noradrenaline. The present study therefore investigated whether selective agonism of α4β2 or α7 nicotinic acetylcholine receptors would affect the mouse forced swim test activity of two antidepressants with distinct mechanisms of action, namely the selective serotonin reuptake inhibitor citalopram and the no... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466955 Thu, 01 Dec 2011 05:00:00 +0100 5466955 http://www.medworm.com/index.php?rid=5466954&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1344%3Frss%3D1 High lipoprotein(a) (Lp(a)) levels constitute a major risk factor for vascular mortality. Major depression also increases the risk of cardiovascular disease. We measured the concentrations of Lp(a) in depressed patients and controls and studied the effects of antidepressant treatment and treatment outcome. Lp(a) levels were analysed at baseline in 35 in-patients with DSM-IV major depression who were then treated in a randomized double-blind manner with amitriptyline (n = 14) or paroxetine (n = 21), as well as in 33 healthy controls. Lp(a) levels were re-assessed after 4 weeks of treatment. We found a significant decrease in Lp(a) in patients treated with paroxetine, but not in those treated with amitriptyline. Our results suggest that antidepressant treatment with paroxetine might contribu... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466954 Thu, 01 Dec 2011 05:00:00 +0100 5466954 http://www.medworm.com/index.php?rid=5466953&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1337%3Frss%3D1 This study compared the effects of ATD on mood, cognitive function and motor function in two groups of healthy volunteers, one group aged 50–69 and the other aged 70–89. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, crossover, randomized design. The effects of ATD were not significantly different between age groups, suggesting that there is relatively little functional change across these age ranges. Compared with studies in much younger age groups there was, however, more evidence of an adverse effect of ATD on psychomotor function and working memory. There was no effect of ATD on mood despite inclusion of subjects with a family history of depression. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466953 Thu, 01 Dec 2011 05:00:00 +0100 5466953 http://www.medworm.com/index.php?rid=5466952&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1329%3Frss%3D1 In conclusion, this preliminary study does not support the involvement of ventral dopaminergic neurotransmission in the antidepressant effects of fluoxetine or psychodynamic psychotherapy. The effects of fluoxetine on thalamic dopamine systems need to be further explored. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466952 Thu, 01 Dec 2011 05:00:00 +0100 5466952 http://www.medworm.com/index.php?rid=5466951&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1320%3Frss%3D1 Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked with depressive symptoms among adults in various clinical settings. Data in generally healthy, community-dwelling individuals remain inconclusive. We investigated whether depression was associated with 25(OH)D and/or PTH in a sample of middle-aged and older men (n = 3369; mean age 60 ± 11) participating in the European Male Ageing Study, and whether any associations were explained by lifestyle and health factors. The Beck Depression Inventory-II (BDI-II) was used to screen for depression, and serum 25(OH)D and PTH levels measured by radioimmunoassay. Univariate analysis revealed that 25(OH)D levels were lower (p < 0.001) and PTH higher (p = 0.004) in people with depression. In a... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466951 Thu, 01 Dec 2011 05:00:00 +0100 5466951 http://www.medworm.com/index.php?rid=5466950&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1313%3Frss%3D1 The neuropeptide oxytocin has been implicated in a wide range of social processes, such as pair bonding, affiliation, and social judgments that may contribute to normal adjustment and psychiatric states. The present experimental study sought to elucidate potential underlying mechanisms by which oxytocin may impact social processes by examining the effects of intranasal oxytocin on basic evaluative processes. Subjects rated slide stimuli from the International Affective Picture System, varying across multiple categories (pleasant, neutral, unpleasant) and social content. Separate ratings for arousal and for the positive and negative components of valence were obtained in the context of a bivariate evaluative space model. Oxytocin did not have an independent significant effect on positivity ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466950 Thu, 01 Dec 2011 05:00:00 +0100 5466950 http://www.medworm.com/index.php?rid=5466949&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1304%3Frss%3D1 Animal models of depression support a pathogenetic role for vasopressinergic activation involving increased arginine vasopressin (AVP) release and AVP receptor (V1b) synthesis. Evidence of this has been found particularly in patients with highly anxious-retarded (HAR) and above-normal AVP (ANA) depression. A general pathogenetic theory however predicts vasopressinergic activities to play a role in at least all major depressive disorders, and antidepressant (AD) treatment to be mediated by vasopressinergic reduction. We tested these hypotheses by re-analysing the data of 66 depressed patients; 27 with and 39 without AD treatment. The plasma AVP concentration and the AVP-cortisol correlation were used as presumed parameters of AVP release and pituitary V1b receptor function. A high AVP-corti... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466949 Thu, 01 Dec 2011 05:00:00 +0100 5466949 http://www.medworm.com/index.php?rid=5466948&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1295%3Frss%3D1 Affective disorders are among the main causes of disability worldwide, yet the underlying pathophysiology remains poorly understood. Recently, landmark neuroimaging studies have shown increased metabolic activity in Brodmann Area 25 (BA25) in depressed patients. Moreover, functional inactivation of this region using deep brain stimulation alleviated depressive symptoms in severely depressed patients. Thus, we examined the effect of a similar manipulation, pharmacological inactivation of the infralimbic cortex, the rodent correlate of BA25, in an animal model of antidepressant activity: the modified rat forced swim test. Transient inactivation of the infralimbic cortex using muscimol reduced immobility, an antidepressant-like effect in the test. Importantly, this activity was not the result... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466948 Thu, 01 Dec 2011 05:00:00 +0100 5466948 http://www.medworm.com/index.php?rid=5466947&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1289%3Frss%3D1 Recent published data and treatment guidelines have created uncertainty about the use of lamotrigine in affective disorders, especially in acute bipolar depression. Furthermore, unpublished data on lamotrigine in mania, mixed episodes, unipolar depression and rapid cycling are still waiting to be integrated into the literature. Therefore, we critically reviewed the position of lamotrigine in the acute and long-term treatment of affective disorders. Studies were identified by searching English language articles published in MEDLINE using the key words: lamotrigine, bipolar depression, unipolar depression, mania, mixed episode, long-term treatment, rapid-cycling. Results of unpublished trials were obtained from the GlaxoSmithKline website. Lamotrigine showed efficacy in the prophylaxis of bi... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466947 Thu, 01 Dec 2011 05:00:00 +0100 5466947 http://www.medworm.com/index.php?rid=5466946&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1277%3Frss%3D1 We present results showing that re-analysing the same data using more appropriate methods leads to substantially different conclusions. However, we also believe that psychopharmacology has lessons to learn from the Kirsch et al. paper. We discuss issues surrounding the interpretation of clinical trials of antidepressants, including the difficulties of extrapolating from randomized controlled trials to the clinic, and the question of failed trials. We call for more research to establish the effectiveness of antidepressants in clinically relevant populations under naturalistic conditions, for example, in relapse prevention, in patients with co-morbidities, and in primary care settings. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466946 Thu, 01 Dec 2011 05:00:00 +0100 5466946 http://www.medworm.com/index.php?rid=5466945&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F10%2F1269%3Frss%3D1 Despite an increasingly recognized relationship between depression and smoking, little is known about the degree to which treatment studies for depression consider the impact of smoking on outcomes. The aim of this study is to examine the extent to which smoking is considered in current antidepressant treatment research. We conducted a MEDLINE search of recent randomized clinical trials of pharmacotherapy for depression published between 1 January and 31 December 2007, and a search of current pharmacological intervention studies for depression using www.ClinicalTrials.gov. Only 5% of the 107 pharmacological trials for depression published in 2007 reported the smoking status of their samples. Two studies (1.9%) controlled for smoking in the analyses and no studies analyzed outcomes by smoki... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5466945 Thu, 01 Dec 2011 05:00:00 +0100 5466945 http://www.medworm.com/index.php?rid=5312329&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1256%3Frss%3D1 In conclusion, the study extends the well-documented finding in animals of the attenuating effect of scopolamine on hippocampal activity during allocentric spatial memory to humans. Furthermore, the results call for further investigation of the dissociation between the hippocampal and neostriatal memory systems during allocentric spatial processing under cholinergic blockade in humans. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312329 Wed, 12 Oct 2011 04:00:00 +0100 5312329 http://www.medworm.com/index.php?rid=5312328&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1235%3Frss%3D1 Several theoretical frameworks have been developed to understand putative processes and mechanisms involved in addiction. Whilst these ‘theories of addiction’ disagree about importance and/or nature of a number of key psychological processes (e.g. the necessity of craving and/or the involvement of drug-value representations), a number of commonalities exist. For instance, it is widely accepted that Pavlovian associations between cues and environmental contexts and the drug effects acquired over the course of addiction play a critical role, especially in relapse vulnerability in detoxified addicts. Additionally, all theories of addiction (explicitly or implicitly) propose that chronic drug exposure produces persistent neuroplastic changes in neurobiological circuitries underlyin... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312328 Wed, 12 Oct 2011 04:00:00 +0100 5312328 http://www.medworm.com/index.php?rid=5312327&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1226%3Frss%3D1 The study of sleep is a useful approach to studying the brain in psychiatric disorders and in investigating the effects of psychotropic drugs. Sleep physiology lends itself well to pharmacological and physiological manipulation, as it has the advantage of a functional output, the electroencephalograph, which is common to all mammals, and can be measured in freely moving (or naturally sleeping) animals under controlled laboratory conditions or in a naturalistic home environment. The complexity of sleep architecture varies between species but all share features which are comparable. In addition, sleep architecture is sensitive to changes in brain neurotransmitters such as serotonin, so cross-species sleep measurement can be combined with pharmacological manipulation to investigate the recept... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312327 Wed, 12 Oct 2011 04:00:00 +0100 5312327 http://www.medworm.com/index.php?rid=5312326&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1207%3Frss%3D1 This article evaluates the possibility that cognitive and physiological abnormalities in schizophrenia can be used as central nervous system biomarkers to predict, in healthy volunteers, the likely efficacy of entirely new pharmacological approaches to treatment. Early detection of efficacy would focus resource on rapidly developing, effective drugs. We review the relevance of selected cognitive and physiological abnormalities as biomarkers in schizophrenia and three of its surrogate populations: (i) healthy volunteers with high trait schizotypy; (ii) unaffected relatives of patients; and (iii) healthy volunteers in a state of cortical glutamate disinhibition induced by low-dose ketamine. Several biomarkers are abnormal in these groups and in some instances there has been exploratory work ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312326 Wed, 12 Oct 2011 04:00:00 +0100 5312326 http://www.medworm.com/index.php?rid=5312325&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1199%3Frss%3D1 We have validated the use of prolonged inhalation of 7.5% carbon dioxide (CO2) as a human model of anxiety and have shown that drugs from two prototypical classes of anxiolytics, benzodiazepines and a serotonin reuptake inhibitor, attenuate CO2-induced symptoms (Bailey et al., 2007a). Preclinical evidence suggests that drugs acting at the corticotropin-releasing factor (CRF) system may be useful for the treatment of depression, anxiety, and other stress-related disorders (Valdez, 2006), hence we have now examined the effects of a CRF1 receptor antagonist in the 7.5% CO2 model. In a randomized double-blind, placebo-controlled, study in 32 healthy participants we examined the effects of 7 days of treatment with the CRF1 receptor antagonist, R317573, at a dose that shows a favourable safety p... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312325 Wed, 12 Oct 2011 04:00:00 +0100 5312325 http://www.medworm.com/index.php?rid=5312324&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1192%3Frss%3D1 Anxiety is a complex phenomenon that can represent contextually different experiences to individuals. The experimental modelling in healthy volunteers of clinical anxiety experienced by patients is challenging. Furthermore, defining when and why anxiety (which is adaptive) becomes an anxiety disorder (and hence maladaptive) is the subject of much of the published literature. Observations from animal studies can be helpful in deriving mechanistic models, but gathering evidence from patients and reverse translating this to healthy volunteers and thence back to laboratory models is a more powerful approach and is likely to more closely model the clinical disorder. Thus the development and validation of a robust healthy volunteer model of anxiety may help to bridge the gap between the laborato... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312324 Wed, 12 Oct 2011 04:00:00 +0100 5312324 http://www.medworm.com/index.php?rid=5312323&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1175%3Frss%3D1 A major issue in proof of concept studies and early clinical trials of novel therapeutic agents is that the active drugs can often have a relatively small additional effect compared with placebo. This is especially the case in psychiatry when we usually have no direct method of measuring the pathology underlying the disorder being studied but, rather, have to rely on the subjective assessment of psychiatric symptoms. The use of the electroencephalogram (EEG) offers two potential major means of addressing this problem. First it is able to provide direct data relating to neural activity that may be abnormal in certain disorders. As such there are opportunities for utilizing the EEG in a variety of ways as an objective outcome measure. Second there is growing evidence that in certain circumst... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312323 Wed, 12 Oct 2011 04:00:00 +0100 5312323 http://www.medworm.com/index.php?rid=5312322&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1168%3Frss%3D1 Investigating pharmacological modulation of brain activity using magnetic resonance imaging (MRI) presents an exciting opportunity to bridge the gap between preclinical and clinical studies, and holds the potential to be a useful tool in the discovery and development of novel therapeutic agents. Most functional MRI studies to date have utilized the blood oxygen level dependent (BOLD) contrast mechanism. Although this has some advantages over other techniques and is widely available, BOLD has two significant limitations for the study of drug effects; it is an indirect measurement of neuronal function, and produces only a relative (non-quantitative) measure of blood dynamics. Here we describe the various experimental manipulations that have been used to reduce the impact of these limitations... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312322 Wed, 12 Oct 2011 04:00:00 +0100 5312322 http://www.medworm.com/index.php?rid=5312321&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1159%3Frss%3D1 Agomelatine is a new antidepressant with a novel profile of pharmacological action. The clinical efficacy of agomelatine has been established in major depression, but its actions on emotional bias are unknown. Consequently, the current experimental study assessed the effect of agomelatine on emotional processing in healthy volunteers using an Emotional Test Battery shown to be sensitive to serotonin and noradrenaline reuptake inhibitors. Volunteers were randomized to receive placebo, 25 mg or 50 mg of agomelatine over a 7-day period in a double-blind parallel groups design. Emotional processing (n = 48) was assessed on the morning of day 8 using the Emotional Test Battery which included facial expression recognition, emotional memory, attentional visual probe and emotion-potentiated startl... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312321 Wed, 12 Oct 2011 04:00:00 +0100 5312321 http://www.medworm.com/index.php?rid=5312320&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F9%2F1148%3Frss%3D1 Current antidepressant agents are similar in efficacy to the original drugs discovered in the 1950s. The development of new treatments for depression is, however, limited by the absence of validated human biomarker models to predict efficacy, clinical profile and dosing. Such models need to meet key criteria for biomarkers including sensitivity, specificity and relevance to depression. Here we review studies exploring whether early changes in emotional processing with antidepressant drug administration meet these criteria. A large body of evidence suggests that changes in emotional memory are particularly relevant to depression and to antidepressant drug action whereas changes in attentional processing are sensitive to anxiolytic drugs. These tasks are not consistently affected by agents w... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312320 Wed, 12 Oct 2011 04:00:00 +0100 5312320 http://www.medworm.com/index.php?rid=5312319&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F9%2F1145%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5312319 Wed, 12 Oct 2011 04:00:00 +0100 5312319 http://www.medworm.com/index.php?rid=5158334&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1030%3Frss%3D1 An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and accordingly treatment with GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, GABA-A antagonists are also convulsant which preclude their use for therapeutic intervention in DS individuals. Here, we have evaluated safer strategies to release GABAergic inhibition using a GABA-A-benzodiazepine receptor inverse agonist selective for the α5-subtype (α5IA). We demonstrate that &a... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5158334 Tue, 09 Aug 2011 23:00:00 +0100 5158334 http://www.medworm.com/index.php?rid=5118443&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1134%3Frss%3D1 Smoking rates among depressed individuals are higher than is observed in the background population, and nicotine alleviates depressive symptoms. In rodents, nicotine shows antidepressant-like effects in the forced swim and learned helplessness paradigms. Clinical depression is associated with both anhedonia and cognitive impairments. In rats, chronic mild stress (CMS) decreases voluntary sucrose intake, reflecting an anhedonic-like state, and impairs performance in the spontaneous alternation behaviour (SAB) test, suggesting impaired cognitive function. Here, we examine the effect of chronic treatment of nicotine (0.4 mg/kg/day) and sertraline (5 mg/kg/day) on CMS-induced anhedonic-like behaviour and impairment in the SAB test. Nicotine and sertraline administered individually or in combin... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118443 Tue, 09 Aug 2011 23:00:00 +0100 5118443 http://www.medworm.com/index.php?rid=5118442&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1126%3Frss%3D1 Involvement of the dopamine D1 and D2 receptors in the nucleus accumbens (NAc) with interaction between morphine and nicotine on inhibitory avoidance (IA) memory was investigated. A step-through type of inhibitory avoidance tasks was used to assess memory in male Wistar rats. The results showed that subcutaneous (s.c.) administration of morphine (7.5 mg/kg) after training decreased retrieval of IA memory in the animals when tested 24 h later. Pre-test administration of the same dose of morphine significantly reversed the deficiency in retrieval. The results also showed that pre-test administration of nicotine (0.2 and 0.4 mg/kg, s.c.) by itself mimicked the effect of pre-test morphine, and lower doses of nicotine (0.1 and 0.2 mg/kg) also improved the effect of a low dose of morphine (2.5 m... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118442 Tue, 09 Aug 2011 23:00:00 +0100 5118442 http://www.medworm.com/index.php?rid=5118441&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1118%3Frss%3D1 In this study, we tested the in vivo effects of melatonin on these Alzheimer-like changes. We found that administration of melatonin intraperitoneally for 9 consecutive days before injection of calyculin A could prevent calyculin A-induced synaptophysin loss, memory retention deficits, as well as hyperphosphorylation of tau and neurofilaments. Furthermore, melatonin partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307 (Y307), a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde, a marker of oxidative stress, induced by calyculin A. These results suggest that melatonin could serve as a potential therapeutic agent for preventing Alzheimer-like pathological changes and behavioral abnormality via modulati... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118441 Tue, 09 Aug 2011 23:00:00 +0100 5118441 http://www.medworm.com/index.php?rid=5118440&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1101%3Frss%3D1 Tetrahydro-N, N-dimethyl-2, 2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) binds to muscarinic acetylcholine and sigma1 (1) receptors with affinities in the low micromolar range. We characterized its anti-amnesic and neuroprotective potentials in pharmacological and pathological amnesia models. Spatial working memory was evaluated using spontaneous alternation in the Y-maze and non-spatial memory using passive avoidance procedures. ANAVEX2-73 (0.01–3.0 mg/kg i.p.) alleviated the scopolamine- and dizocilpine-induced learning impairments. ANAVEX2-73 (300 µg/kg) also reversed the learning deficits in mice injected with Aβ25-35 peptide, a non-transgenic Alzheimer’s disease model. When the drug was injected simultaneously with Aβ25-35, 7 days before th... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118440 Tue, 09 Aug 2011 23:00:00 +0100 5118440 http://www.medworm.com/index.php?rid=5118439&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1088%3Frss%3D1 Extracts of sage (Salvia officinalis/lavandulaefolia) with terpenoid constituents have previously been shown to inhibit cholinesterase and improve cognitive function. The current study combined an in vitro investigation of the cholinesterase inhibitory properties and phytochemical constituents of a S. lavandulaefolia essential oil, with a double-blind, placebo-controlled, balanced crossover study assessing the effects of a single dose on cognitive performance and mood. In this latter investigation 36 healthy participants received capsules containing either 50 µL of the essential oil or placebo on separate occasions, 7 days apart. Cognitive function was assessed using a selection of computerized memory and attention tasks and the Cognitive Demand Battery before the treatment and ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118439 Tue, 09 Aug 2011 23:00:00 +0100 5118439 http://www.medworm.com/index.php?rid=5118438&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1076%3Frss%3D1 It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118438 Tue, 09 Aug 2011 23:00:00 +0100 5118438 http://www.medworm.com/index.php?rid=5118437&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1062%3Frss%3D1 An initial standardized approach for combining neuropsychological and neurophysiological measures in order to assess the neurocognitive effects of drugs in groups and individuals is introduced. Its application is illustrated with sedatives, antiepileptic drugs, psychostimulants, antihistamines, and intoxicants. Task performance, electroencephalography, and evoked potential measures during computerized attention and memory testing that are most sensitive to drug effects are identified in a sample population and then applied to individuals. In six example exploratory studies, drug effects were detected with an average area under curve (AUC) of 0.97 (p < 0.0001; 95% sensitivity, 96% specificity). In 10 example validation studies with other drugs and/or different subjects and populations, d... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118437 Tue, 09 Aug 2011 23:00:00 +0100 5118437 http://www.medworm.com/index.php?rid=5118436&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1053%3Frss%3D1 The aim of the present study was to identify the neural substrate underlying memory impairment due to a single dose of MDMA (3,4-methylenedioxymethamphetamine) by means of pharmaco-MRI. Based on previous behavioral results it was hypothesized that this deficit could be attributed to a specific influence of MDMA on encoding. Fourteen Ecstasy users participated in this double-blind, placebo-controlled, within-subject study with two treatment conditions: MDMA (75 mg) and placebo. Memory performance was tested by means of a word learning task including two words lists, one addressing reading processes (control task, CWL) and a second (experimental task, EWL) addressing encoding and reading processes. Behavioral data showed that under the influence of MDMA, EWL performance was worse than placeb... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118436 Tue, 09 Aug 2011 23:00:00 +0100 5118436 http://www.medworm.com/index.php?rid=5118435&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1043%3Frss%3D1 The present study was undertaken to examine effects of self-administered MDMA on novel object exploration (NOR) memory. Self-administration was conducted during daily 2 h tests that continued until a total of 165 mg/kg was self-administered (range = 13–41 days for individual rats). Control rats were placed in the self-administration boxes during daily sessions but did not receive any drug. One or 10 weeks following the last self-administration session, memory was assessed using a standard NOR task. When exploration time was used as the dependent measure for the control rats, there was no consistent pattern of change as a function of inter-trial interval (ITI) and exploration times failed to reveal decay in the function relating exploration to ITI. When number of approaches was examin... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118435 Tue, 09 Aug 2011 23:00:00 +0100 5118435 http://www.medworm.com/index.php?rid=5118434&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1030%3Frss%3D1 An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and accordingly treatment with GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, GABA-A antagonists are also convulsant which preclude their use for therapeutic intervention in DS individuals. Here, we have evaluated safer strategies to release GABAergic inhibition using a GABA-A-benzodiazepine receptor inverse agonist selective for the α5-subtype (α5IA). We demonstrate that α5IA restores learning and memory functions of Ts65Dn mice in the novel-objec... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118434 Tue, 09 Aug 2011 23:00:00 +0100 5118434 http://www.medworm.com/index.php?rid=5118433&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F1020%3Frss%3D1 The objective of this study was to assess the safety, tolerability and efficacy of TC-1734 (AZD3480), a selective α4β2 nicotinic agonist, in the treatment of age-associated memory impairment. A randomized placebo-controlled trial was conducted in 16 community-based centers within the USA. Subjects who met objective criteria for age-associated memory impairment were recruited between November 2004 and December 2005. Subjects were randomly assigned to receive orally 25 mg (n = 59), 50 mg (n = 68) TC-1734 (AZD3480) or placebo (n = 66) in a double-blind fashion for 16 weeks. Main outcome measures included routine clinical safety measures, tolerability, cognitive assessment via the Cognitive Drug Research computerized test battery and a Subject Global Impression Scale of Cognition (S... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118433 Tue, 09 Aug 2011 23:00:00 +0100 5118433 http://www.medworm.com/index.php?rid=5118432&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F8%2F997%3Frss%3D1 The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer’s disease (A) and memantine for moderate to severe Alzheimer’... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5118432 Tue, 09 Aug 2011 23:00:00 +0100 5118432 http://www.medworm.com/index.php?rid=5036022&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F982%3Frss%3D1 It has been reported that neuropeptide Y (NPY) contributes to the behavioral response of amphetamine (AMPH), a psychostimulant. The present study examined whether protein kinase C (PKC)- signaling was involved in this action. Moreover, possible roles of glutathione peroxidase (GP) and melanocortin receptor 4 (MC4R) were also examined. Rats were given AMPH daily for 4 days. Hypothalamic NPY, PKC, GP and MC4R were determined and compared. Pretreatment with α-methyl-para-tyrosine could block AMPH-induced anorexia, revealing that endogenous catecholamine was involved in regulating AMPH anorexia. PKC, GP and MC4R were increased with maximal response on Day 2 during AMPH treatment, which were concomitant with the decreases in NPY. cAMP response element binding protein (CREB) DNA binding ac... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036022 Thu, 14 Jul 2011 23:00:00 +0100 5036022 http://www.medworm.com/index.php?rid=5036021&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F976%3Frss%3D1 In conclusion, relatively short-term hyperhomocysteinemia in mice does not reproduce or lead to alterations reported in one-carbon metabolism in disorders associated with lifelong elevated plasma homocysteine. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036021 Thu, 14 Jul 2011 23:00:00 +0100 5036021 http://www.medworm.com/index.php?rid=5036020&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F960%3Frss%3D1 The sigma-1 (1) protein regulates calcium homeostasis and acts as an endoplasmic reticulum chaperone. It can be activated by ligands which impact memory, depression, anxiety or addiction processes. We here characterized the behavioural phenotype of knockout (KO) mice for the 1 protein. Two-month old male 1 –/– mice showed signs of anxiety in the open-field, passive avoidance or elevated plus-maze test, but other activity or memory responses were unchanged. Female 1 –/– mice showed deficits in spontaneous alternation or water-maze learning. Twelve-month old 1 +/– female mice showed deficits in alternation and 1 –/– mice in avoidance escape latency. Two- and 14-month old female 1 –/– mice showed decrease... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036020 Thu, 14 Jul 2011 23:00:00 +0100 5036020 http://www.medworm.com/index.php?rid=5036019&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F952%3Frss%3D1 The role of the serotonin (5-HT) system in the neurobiology and treatment of panic disorder (PD) remains unproven. Previously we detected lower brain 5-HT transporter (SERT) availability in PD, but the findings were preliminary and mainly limited to female patients. The aim of this study was to assess non-displaceable brain SERT binding potential (BP ND) in male and female patients with PD. The SERT BP ND was measured in groups of patients with PD (five males and six females) and matched healthy control subjects (12 males and 12 females) using positron emission tomography (PET) and [11C]MADAM tracer. SERT BP ND were significantly higher in 13 of 20 studied brain regions, including several cortical and raphe areas, but lower in the hippocampus in males with PD as compar... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036019 Thu, 14 Jul 2011 23:00:00 +0100 5036019 http://www.medworm.com/index.php?rid=5036018&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F944%3Frss%3D1 Serotonin plays a role in reinforcement learning; however, it is not known which serotonin receptors mediate these effects. Serotonin 6 (5-HT6) receptors are abundant in the striatum, a brain area that is involved in reinforcement learning. We previously found that 5-HT6 receptors in the dorsomedial striatum (DMS) affect reinforcement learning or consolidation over several days. We use viral-mediated gene transfer to discern the role that 5-HT6 receptors play in mediating post-synaptic responses in anterior versus posterior DMS. Male Long-Evans rats were used to study learning acquisition during a single session of 100 trials on a fixed interval of 20 seconds. In a discrete action–outcome learning task, rats had 10 seconds to press a lever to induce lever retraction and sucrose pelle... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036018 Thu, 14 Jul 2011 23:00:00 +0100 5036018 http://www.medworm.com/index.php?rid=5036017&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F934%3Frss%3D1 Reduced functioning of the dopamine transporter (DAT) has been linked to bipolar disorder (BD). Mice with reduced DAT functioning (knockdown, KD) exhibit a behavioral profile in the mouse Behavioral Pattern Monitor (BPM) consistent with patients with BD mania in the human BPM. Patients with BD also exhibit increased risk taking, which can be quantified using the Iowa Gambling Task (IGT). We hypothesized that DAT KD mice would exhibit increased risk-taking behavior in a novel mouse version of the IGT. DAT KD and wildtype (WT) littermates were trained in the mouse IGT. In session 1, KD mice initially made riskier choices, but later performed comparably to WT mice. Once trained to stable choice performance, DAT KD mice continued to exhibit a trend to choose the riskier options more than WT mi... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036017 Thu, 14 Jul 2011 23:00:00 +0100 5036017 http://www.medworm.com/index.php?rid=5036016&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F924%3Frss%3D1 Bipolar disorder has been associated with disturbances in circadian rhythms. Lithium is frequently used in the long-term treatment of bipolar disorder, and has been shown to prolong such rhythms in animals and humans. To examine whether lithium affects the expression of genes regulating the circadian clock, cultured NIH-3T3 cells were synchronized by serum-shocking, and the relative expression of the clock genes Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Brain and muscle aryl hydrocarbon nuclear translocator-like 1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-Erb-α (Nr1d1), RAR-related orphan receptor α (Ror-α), Glycogen synthase kinase-3β (Gsk-3β), Casein kinase 1– (CK1-; Csnk1), E4 binding... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036016 Thu, 14 Jul 2011 23:00:00 +0100 5036016 http://www.medworm.com/index.php?rid=5036015&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F915%3Frss%3D1 We present data on 1450 adolescents from the Ten Towns Heart Health Study (TTHHS) extensively phenotyped for smoking-related traits during adolescence. Single nucleotide polymorphisms from CHRNA5 and CHRNA3 (previously associated with smoking), were typed in our study population, previously genotyped for CYP2A6. Association analyses between each genotype and both smoking status and behavioural markers of smoking were performed. rs16969968 in CHRNA5 was associated both at 13–15 years and 18 years with current smoking amongst adolescents who had tried smoking (OR = 1.82, CI = 1.10–3.01, p = 0.02 at age 13–15; OR = 2.39, CI = 1.37–4.17, p = 0.002 at age 18). No association was found for rs578776 in CHRNA3. The effects of CHRNA5 and CYP2A6 genotypes in TTHHS appeared to... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036015 Thu, 14 Jul 2011 23:00:00 +0100 5036015 http://www.medworm.com/index.php?rid=5036014&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F908%3Frss%3D1 The CYP2D6 enzyme is a capacity-limited high-affinity drug elimination pathway that metabolizes numerous psychiatric medicines. The capacity-limited nature of this enzyme suggests that drug dose may serve as an important factor that influence genotype–phenotype associations. However, dose dependency of CYP2D6 genotype contributions to drug elimination, and its interaction with environmental factors (e.g., smoking) did not receive adequate attention in translational study designs. Fluvoxamine is a selective serotonin reuptake inhibitor antidepressant. Fluvoxamine concentration is one of the factors previously linked to clinical remission in moderate to severe depression. We investigated the joint effect of smoking (an inducer of CYP1A2) and CYP2D6 genotype on interindividual variabili... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036014 Thu, 14 Jul 2011 23:00:00 +0100 5036014 http://www.medworm.com/index.php?rid=5036013&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F896%3Frss%3D1 This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the PANSS total ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036013 Thu, 14 Jul 2011 23:00:00 +0100 5036013 http://www.medworm.com/index.php?rid=5036012&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F888%3Frss%3D1 We report the first controlled catecholamine study in 22q11DS-related schizophrenia. Twelve adults with 22q11DS with schizophrenia (SCZ+) and 22 adults with 22q11DS without schizophrenia (SCZ-) were genotyped for the COMT Val108/158 Met genotype. We assessed dopaminergic markers in urine and plasma. We also correlated these markers with scores on the Positive and Negative Symptom Scale (PANSS). Contrary to our expectations, we found SCZ+ subjects to be more often Val hemizygous and SCZ- subjects more often Met hemizygous. Significant COMT cross gender interactions were found on dopaminergic markers. In SCZ+ subjects there was a negative correlation between prolactin levels and scores on the general psychopathology subscale of the PANSS scores. These findings suggest intriguing, but complex... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036012 Thu, 14 Jul 2011 23:00:00 +0100 5036012 http://www.medworm.com/index.php?rid=5036011&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F875%3Frss%3D1 Homer1a is a glutamate-related gene whose expression is induced by antipsychotics acutely (i.e. 90 min after treatment). Acute Homer1a expression is preserved after prolonged antipsychotic treatments, while the effects of short-term discontinuation after chronic antipsychotic treatment have not yet been assessed. Here, we studied early and long-term effects on gene expression by antipsychotics for Homer1a and other components of glutamatergic synapses. In the first paradigm, we evaluated Homer1a acute expression by single administration of antipsychotics (haloperidol 0.8 mg/kg, ziprasidone 10 and 4 mg/kg, clozapine 15 mg/kg). Haloperidol and ziprasidone induced Homer1a in the striatum. Induction by ziprasidone was dose-dependent. These results suggest that acute Homer1a expression correlat... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036011 Thu, 14 Jul 2011 23:00:00 +0100 5036011 http://www.medworm.com/index.php?rid=5036010&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F867%3Frss%3D1 There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment w... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036010 Thu, 14 Jul 2011 23:00:00 +0100 5036010 http://www.medworm.com/index.php?rid=5036009&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F7%2F857%3Frss%3D1 This study aimed to integrate findings concerning possible endophenotypes modulating between genetic factors and manifested suicidal behaviour. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=5036009 Thu, 14 Jul 2011 23:00:00 +0100 5036009 http://www.medworm.com/index.php?rid=4892403&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F6%2F853%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892403 Tue, 31 May 2011 23:00:00 +0100 4892403 http://www.medworm.com/index.php?rid=4892400&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F6%2F850%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892400 Tue, 31 May 2011 23:00:00 +0100 4892400 http://www.medworm.com/index.php?rid=4892399&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F6%2F848%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892399 Tue, 31 May 2011 23:00:00 +0100 4892399 http://www.medworm.com/index.php?rid=4892398&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Freprint%2F25%2F6%2F846%3Frss%3D1 (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892398 Tue, 31 May 2011 23:00:00 +0100 4892398 http://www.medworm.com/index.php?rid=4892397&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F842%3Frss%3D1 Clozapine is the treatment of choice in refractory schizophrenia. Its more extensive use is limited by adverse effects and the need for regular blood monitoring. However, black patients are disadvantaged with respect to clozapine usage. Lower baseline Absolute Neutrophil Count compared with Whites leads to a greater frequency of blood testing, treatment interruptions and discontinuation. This may in part be explained by Benign Ethnic Neutropenia, but too few black patients are thus registered. The four cases described in this report underline some of the difficulties if this problem is under-recognized. Moreover, in our sample of 191 clozapine recipients in an inner London hospital, black patients account for approximately half, but only a small proportion, 8/95 (8.4%) are registered as ha... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892397 Tue, 31 May 2011 23:00:00 +0100 4892397 http://www.medworm.com/index.php?rid=4892396&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F836%3Frss%3D1 Our laboratory and others have reported that Brattleboro (BRAT) rats, a Long Evans (LE) strain with a single gene mutation, have inherent deficits in prepulse inhibition (PPI) homologous to those observed in schizophrenia patients and that these deficits are reversed by antipsychotic drugs (APDs). To further evaluate the potential predictive validity of BRAT rat PPI for APDs, we compared the effects of acute subcutaneous administration of the typical APD chlorpromazine to that of three psychotropic drugs without antipsychotic efficacy, the antidepressant imipramine, the anxiolytic diazepam and the anticonvulsant mood stabilizer valproic acid on male and female BRAT rat PPI. Male and female BRAT rats exhibited baseline (saline treatment) PPI that was not different from each other (21.1% and... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892396 Tue, 31 May 2011 23:00:00 +0100 4892396 http://www.medworm.com/index.php?rid=4892395&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F822%3Frss%3D1 In this study, we investigated for the first time the effects of antipsychotics on abnormal behaviours observed in prenatally MAM-exposed rats. We first examined spontaneous and MK-801-induced locomotor activity in an open field in adult E17 MAM- or saline-exposed rats. Then, the effect of single injections of haloperidol, clozapine and risperidone was investigated in MAM- or sham-exposed rats on spontaneous and MK-801 (0.05 mg/kg)-induced hyperactivity. Risperidone more selectively counteracted the spontaneous hyperactivity in MAM than in sham rats, while haloperidol and clozapine induced similar effects on spontaneous locomotion in both groups. The main result of this study is that all the tested antipsychotics were more effective in attenuating the MK-801-induced hyperlocomotion in MAM ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892395 Tue, 31 May 2011 23:00:00 +0100 4892395 http://www.medworm.com/index.php?rid=4892394&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F808%3Frss%3D1 Previously, we showed that NMDA antagonists enhance high-frequency oscillations (130–180 Hz) in the nucleus accumbens. However, whether NMDA antagonists can enhance high-frequency oscillations in other brain regions remains unclear. Here, we used monopolar, bipolar and inverse current source density techniques to examine oscillatory activity in the hippocampus, a region known to generate spontaneous ripples (~200 Hz), its surrounding tissue, and the dorsal striatum, neuroanatomically related to the nucleus accumbens. In monopolar recordings, ketamine-induced increases in the power of high-frequency oscillations were detected in all structures, although the power was always substantially larger in the nucleus accumbens. In bipolar recordings, considered to remove common-mode input, hi... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892394 Tue, 31 May 2011 23:00:00 +0100 4892394 http://www.medworm.com/index.php?rid=4892393&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F801%3Frss%3D1 Aripiprazole is a unique antipsychotic that seems to act as a partial agonist at dopamine D2-receptors, contrasting with other drugs in this class, which are silent antagonists. Aripiprazole may also bind to serotonin receptors. Both neurotransmitters may play major roles in aversion-, anxiety- and panic-related behaviours. Thus, the present work tested the hypothesis that this antipsychotic could also have anti-aversive properties. Male Wistar rats received injections of aripiprazole (0.1–10 mg/kg) and were tested in the open field, in the elevated plus and T mazes (EPM and ETM, respectively) and in a contextual fear conditioning paradigm. Aripiprazole (1 mg/kg) increased the percentage of entries onto the open arms of the EPM and attenuated escape responses in the ETM. In the latte... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892393 Tue, 31 May 2011 23:00:00 +0100 4892393 http://www.medworm.com/index.php?rid=4892392&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F792%3Frss%3D1 This study investigated the effects of the dopamine D4 receptor agonist, PD168077, on recognition memory using a novel object recognition task, which detects disruption and improvement of recognition memory in rats by measuring their ability to discriminate between familiar and novel objects. When acquisition and test were 6 h apart (experiment 1), control rats failed to discriminate between familiar and novel objects at test. Rats given low doses of PD168077 (0.3; 1.0 mg/kg) also failed to discriminate between the objects, while rats given higher doses (3.0; 10.0 mg/kg) explored the novel object more than the familiar object, indicating retained memory of the familiar object. Thus, at higher doses, PD168077 improved recognition memory in rats. Experiment 2 tested whether PD168077 would at... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892392 Tue, 31 May 2011 23:00:00 +0100 4892392 http://www.medworm.com/index.php?rid=4892391&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F783%3Frss%3D1 Dose–response studies are thought to be a valuable tool to predict the most genetically drug-vulnerable individuals. However, dose–response curves for morphine self-administration have not yet been examined and nor strain differences might be evident. Therefore, this study aimed to define the dose–response curve for morphine self-administration (0.25, 0.5, 1 and 2 mg/kg) in Lewis (LEW) rats and their histocompatible Fischer-344 (F344) rats. In addition, impulsivity has been suggested as one of the genetic factors contributing most to the initiation of drug use. Therefore, the impulsive choice of both rat strains in the presence or absence of the same morphine doses was also analysed. LEW rats self-administered significantly more morphine whatever the dose tested and they ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892391 Tue, 31 May 2011 23:00:00 +0100 4892391 http://www.medworm.com/index.php?rid=4892390&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F774%3Frss%3D1 Our objectives were to (i) estimate lifetime prevalence of psychiatric comorbidity in heroin users and (ii) evaluate psychiatric comorbidity as a predictor of drug-related hospitalization following either (a) methadone maintenance or (b) naltrexone implant treatment. Our method consisted of retrospective, longitudinal follow-up using prospectively collected, state-wide hospital data on two cohorts of heroin-dependent persons (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), first time treated with naltrexone implant (n = 317) or methadone (n = 521) between January 2001 and December 2002. Outcome measures were: (i) prevalence of comorbidity and (ii) changes in risk for drug-related hospitalization – categorized as ‘opioid drugs’, ‘non-opioid dr... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892390 Tue, 31 May 2011 23:00:00 +0100 4892390 http://www.medworm.com/index.php?rid=4892389&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F763%3Frss%3D1 Few unscheduled sedating medications have been evaluated for their subjective and reinforcing effects in humans. To increase the information available about unscheduled sedating medications and to evaluate the ability of human laboratory measures to discriminate between scheduled and unscheduled sedating drugs, 24 subjects with a history of experience with several classes of drugs of abuse, including sedatives and/or alcohol, and who reported liking a test dose of pentobarbital 300 mg, were randomized to single doses of diphenhydramine 400 mg, levetiracetam 4000 mg, valproic acid 1500 mg, diazepam 30 mg or placebo in a double-blind, 5-way crossover study. On the Addiction Research Center Inventory–Morphine-Benzedrine Group and the Next Day Questionnaire measures ‘Take Again&rsq... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892389 Tue, 31 May 2011 23:00:00 +0100 4892389 http://www.medworm.com/index.php?rid=4892388&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F755%3Frss%3D1 This study investigated the relationship between abnormal movements, life events and drug treatment in patients relapsing on antipsychotics with high potency at the dopamine D2 receptor. Twenty-two patients from a cohort of 128 patients experiencing a psychotic relapse were assessed; of these, seven (32%) met criteria for the presence of abnormal involuntary movements. These subjects were found to be clinically distinct from the subjects without abnormal movements. They tended to be older with a greater duration of illness and higher dosage of antipsychotics but more symptoms of psychosis compared with the other subjects. Relapse was also associated with minor life events. The association between abnormal involuntary movements and high levels of psychotic symptoms suggests that dopamine se... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892388 Tue, 31 May 2011 23:00:00 +0100 4892388 http://www.medworm.com/index.php?rid=4892387&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F744%3Frss%3D1 The aim of this study was to investigate the long-term effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders. This was a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiological and 3-year longitudinal intervention programme of first-episode psychosis conducted at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred and seventy-four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 1 year. The primary effectiveness measure was all causes of treatment discontinuation. Effectiveness analyses were based on intend-to-treat populations. In addition, an analysis based on pe... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892387 Tue, 31 May 2011 23:00:00 +0100 4892387 http://www.medworm.com/index.php?rid=4892386&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F734%3Frss%3D1 The aim of this study was to compare 5-HT1A availability in vivo in individuals with schizophrenia before and during treatment with the atypical antipsychotic ziprasidone. Six individuals with schizophrenia underwent two PET scans with [11C]WAY 100635; the first while medication-free (baseline) and the second while taking the atypical antipsychotic ziprasidone (on-medication). Regional volumes of distribution (V T, mL g–1) were derived using a two-tissue compartment kinetic model. Outcome measures included binding potential relative to the plasma (BP P, mL g–1) and the binding potential relative to the nonspecific distribution volume (BP ND, unitless). No significant differences were observed in regional BP P or BP ND with ziprasidone tre... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892386 Tue, 31 May 2011 23:00:00 +0100 4892386 http://www.medworm.com/index.php?rid=4892385&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F722%3Frss%3D1 We employed two event-related functional magnetic resonance imaging tasks using the pictures of mild and intense facial emotions of fear or happiness. The sample comprised 16 chronic schizophrenia patients treated with risperidone long-acting injections (RLAI), 16 patients treated with conventional antipsychotic depots (CONV) and 16 healthy controls (HC). The HC and RLAI groups demonstrated greater activation in the left amygdala in response to intensively fearful faces, and in right cerebellum to intensively happy faces compared with CONV patients. The CONV group demonstrated under-activation in the right temporal pole in response to intensively happy faces (compared with HC) and over-activation in ventro-medial prefrontal cortex (VMPFC) in response to both intensively happy and fearful e... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892385 Tue, 31 May 2011 23:00:00 +0100 4892385 http://www.medworm.com/index.php?rid=4892384&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F715%3Frss%3D1 Antipsychotic drug-induced weight gain and glucose dysregulation add to the cardiovascular risk of patients with schizophrenia and contribute to their early mortality. The currently recommended interventions to address the metabolic complications of antipsychotic drug treatment are to switch the patient from an antipsychotic drug with high metabolic liability to one with a lower liability and to implement lifestyle changes. These interventions can be quite challenging to carry out. So far the progress in improving the metabolic and cardiovascular outcome of patients with major mental illness has been disappointing. We offer an overview of the literature on metformin for antipsychotic drug-induced weight gain and glucose dysregulation and pertinent literature from the Diabetes Prevention Pr... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892384 Tue, 31 May 2011 23:00:00 +0100 4892384 http://www.medworm.com/index.php?rid=4892383&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F6%2F713%3Frss%3D1 Genetics, epigenetics, infection as an environmental factor, functional findings for the immune system, and a therapeutic approach with anti-inflammatory therapy provide evidence for a pivotal role of the immune system in schizophrenia. This field, therefore, should focus more on further schizophrenia research. (Source: Journal of Psychopharmacology) Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4892383 Tue, 31 May 2011 23:00:00 +0100 4892383 http://www.medworm.com/index.php?rid=4733691&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F704%3Frss%3D1 Ethnicity may affect the prescribing of antipsychotic treatment. Previous UK studies conducted in south London have found few differences in antipsychotic prescribing quality for Black and White patients. This larger multicentre study examined the effect of ethnicity on antipsychotic prescribing quality in areas serving the largest proportions of Black patients in the UK. A cross-sectional survey with collection of multiple confounding factors potentially affecting outcomes in eight secondary care units in England over a three month period. Participants were Black or White inpatients prescribed regular antipsychotics on the day of the survey. Antipsychotic dose (expressed as a percentage of licensed maximum), high dose (being prescribed antipsychotic medication above maximum dose), polypha... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733691 Wed, 20 Apr 2011 23:00:00 +0100 4733691 http://www.medworm.com/index.php?rid=4733690&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F698%3Frss%3D1 Studies investigating the relationship between cigarette smoking and prolactin secretion in the general population have yielded inconsistent results. Many antipsychotic drugs increase prolactin secretion, but there are no published studies that have investigated the relationship between smoking and prolactinaemia in antipsychotic-treated patients. We obtained prolactin levels from 228 antipsychotic-treated patients in secondary care mental health services and investigated the relationship between prolactinaemia and cigarette smoking. Twenty-three percent (n = 52) of patients had hyperprolactinaemia. Patients prescribed typical or a combination of typical and atypical antipsychotics had a significantly higher prevalence of hyperprolactinaemia and higher mean prolactin concentration. Both cu... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733690 Wed, 20 Apr 2011 23:00:00 +0100 4733690 http://www.medworm.com/index.php?rid=4733689&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F685%3Frss%3D1 The safety and tolerability of paliperidone palmitate, an injectable atypical antipsychotic agent, were assessed in a 1-year open-label extension of a double-blind study in patients with schizophrenia. Patients from the double-blind study who experienced a recurrence, remained recurrence free until study end, or who were in the transition, maintenance or double-blind phases and had received at least one injection of paliperidone palmitate when enrollment was stopped, were eligible for the open-label extension. Patients received gluteal injections of paliperidone palmitate once every 4 weeks: starting dose 50 mg eq. followed by 25, 50, 75, or 100 mg eq. flexible dosing. Of the 388 patients enrolled, 288 completed the open-label extension. During the open-label extension, the median (range) ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733689 Wed, 20 Apr 2011 23:00:00 +0100 4733689 http://www.medworm.com/index.php?rid=4733688&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F675%3Frss%3D1 Health service providers increasingly need to consider not only the efficacy and safety of a therapy, but also its cost. Our hypothesis was that in our previously reported aripiprazole add-on or switching study, the improved outcomes would be associated with reduced costs. We here report data from this study, now to 52-week follow-up, with 27 total recruits (outpatients partially refractory or intolerant of their current antipsychotic regime). Serial clinical ratings included the Quality of Life Scale and Client Service Receipt Inventory, applied at baseline (N = 24), week 26 (N = 21) and 52 (N = 18). Cost data were unavailable for the drop outs. On last observation carried forward (LOCF) analysis, there was a significant increase in the Quality of Life Scale between baseline and one year ... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733688 Wed, 20 Apr 2011 23:00:00 +0100 4733688 http://www.medworm.com/index.php?rid=4733687&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F667%3Frss%3D1 The persistence of psychotic, affective, cognitive, and psychosocial symptoms despite medications is commonly observed in schizophrenic patients. The present study was a 24-week double-blind, randomized, placebo-controlled trial aimed to explore the efficacy of topiramate add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and cognitive assessments were randomly allocated to receive either up to 200 mg/day of topiramate or a placebo. A final sample of 43 patients completed the study. The results obtained indicate that topiramate appeared to be scarcely effective for reducing clinical symptomatology in schizophrenic patients who have had an incomplete clinical response to cl... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733687 Wed, 20 Apr 2011 23:00:00 +0100 4733687 http://www.medworm.com/index.php?rid=4733686&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F646%3Frss%3D1 The use of second-generation antipsychotics (SGAs) for the treatment of schizophrenia has surged worldwide. Amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole and ziprasidone have now been commonly prescribed. Their effects on QT interval differ but evidence remains sparse and mostly inconclusive. Since prolongation of heart-rate corrected QT interval has been implicated as an useful surrogate marker to predict drug-related cardiac mortality and pro-arrhythmic potentials, it is timely and necessary to compare the effects of Bazett’s corrected QT interval (QTBc) prolongation for the commonly prescribed SGAs. A meta-analysis was conducted according to suggestions by the Quality of Reporting of Meta-analysis group with literature identified using various database... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733686 Wed, 20 Apr 2011 23:00:00 +0100 4733686 http://www.medworm.com/index.php?rid=4733685&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F639%3Frss%3D1 Several analytical approaches were used to characterize time progression of weight changes observed in adults treated with olanzapine from a 12,425-patient database of 86 studies of oral and depot formulations of olanzapine (mean modal dose 13.3 mg/day). Descriptive mean profile plots for completer and modified completer groups showed weight increasing throughout each observed period, with apparent slowing in rate of change after 3 or 4 months. Mixed-effects model repeated measures analyses also showed that weight increased most rapidly early in treatment and slowed within 2 to 4 months. The slowing in rate of change was greatest for patients obese at baseline and least for patients underweight at baseline. This pattern was also observed in a nonparametric regression-based profile. Based o... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733685 Wed, 20 Apr 2011 23:00:00 +0100 4733685 http://www.medworm.com/index.php?rid=4733684&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F630%3Frss%3D1 The relative risk of changes in metabolic parameters during treatment with atypical antipsychotics has not been fully investigated. Baseline-to-endpoint mean and anytime-categorical changes in metabolic parameters were evaluated in Lilly active comparator-controlled clinical trials. Olanzapine-treated patients gained significantly more baseline-to-endpoint weight versus risperidone- (3.3 kg [N = 713; median exposure [ME, days] = 68] versus 1.8 kg [N = 697; ME = 65], p < 0.001), ziprasidone- (2.8 kg [N = 463; ME = 168] versus –1.3 kg [N = 443; ME = 89], p < 0.001), and aripiprazole-treated patients (3.7 kg [N = 273; ME = 104] versus 0.5 kg [N = 275; ME = 187], p < 0.001). Significantly more olanzapine-treated patients gained ≥7% of their baseline weight versus risperidone-... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733684 Wed, 20 Apr 2011 23:00:00 +0100 4733684 http://www.medworm.com/index.php?rid=4733683&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F621%3Frss%3D1 Abnormalities in connectivity are thought to contribute to the symptoms of schizophrenia. Accumulating evidence suggests that antipsychotic medication affects both subcortical and cortical grey and white matter volumes. The goal of this study was to investigate the effects of antipsychotic medication on two white matter tracts: a subcortical-cortical tract, the anterior and posterior limbs of the internal capsule; and a cortical-cortical tract, the corpus callosum. Magnetic resonance imaging was conducted on 10 chronic schizophrenia patients treated with typical antipsychotics and 20 healthy controls at baseline. Patients were switched to olanzapine and both groups were rescanned after 1 year. At baseline, the volume of the anterior limb of the internal capsule was 24% smaller in typical-t... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733683 Wed, 20 Apr 2011 23:00:00 +0100 4733683 http://www.medworm.com/index.php?rid=4733682&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F5%2F567%3Frss%3D1 These guidelines from the British Association for Psychopharmacology address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting, involving experts in schizophrenia and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from the participants and interested parties, and cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. The practice recommendations presented are based on the available evidence to date, and seek to clarify which interventions are of proven benefit. It is hoped that the rec... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4733682 Wed, 20 Apr 2011 23:00:00 +0100 4733682 http://www.medworm.com/index.php?rid=4605707&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F4%2F550%3Frss%3D1 Adenosine is an endogenous purine nucleoside that plays a neuromodulatory role in the central nervous system. A2a adenosine receptors have been involved in reward-related processes, inflammatory phenomena and neurotoxicity reactions. In the present study, we investigated the role of A2a adenosine receptors on the acute pharmacological effects, reinforcement and neuroinflammation induced by MDMA administration. First, the acute effects of MDMA on body temperature, locomotor activity and anxiety-like responses were measured in A2a knockout mice and wild-type littermates. Second, MDMA reinforcing properties were evaluated using the intravenous self-administration paradigm. Finally, we assessed striatal astroglios... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4605707 Thu, 17 Mar 2011 00:00:00 +0100 4605707 http://www.medworm.com/index.php?rid=4605706&cid=s_27156_172_f&fid=27156&url=http%3A%2F%2Fjop.sagepub.com%2Fcgi%2Fcontent%2Fabstract%2F25%2F4%2F538%3Frss%3D1 Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosin... Journal of Psychopharmacology journals http://www.medworm.com/rss/comments.php?id=4605706 Thu, 17 Mar 2011 00:00:00 +0100 4605706