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NEURO 2009 <452> Database EMBASE Accession Number 2009384631 Authors Niehaus J.L. Cruz-Bermudez N.D. Kauer J.A. Institution (Niehaus, Cruz-Bermudez, Kauer) Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI, (Kauer) Department of Neuroscience, Brown University, Providence, RI, (Cruz-Bermudez) Universidad de Puerto Rico, Rio Piedras, (Kauer) Brown University, Box G-B4, Providence, RI 02912, Country of Publication United Kingdom Title Plasticity of addiction: A mesolimbic dopamine short-circuit? Source American Journal on Addictions. 18(4)(pp 259-271), 2009. Date of Publication: July 2009. Publisher Informa Healthcare Abstract The development of drug addiction progresses along a continuum from acute drug use to compulsive use and drug seeking behavior. Many researchers have focused on identifying the physiological mechanisms involved in drug addiction in order to develop effective pharmacotherapies. Neuroplasticity, the putative mechanism underlying learning and memory, is modified by drugs of abuse and may contribute to the development of the eventual addicted state. Innovative treatments directly targeting these drug-induced changes in brain reward components and circuits may be efficacious in reducing drug use and relapse. ISSN 1055-0496 Publication Type Journal: Review Journal Name American Journal on Addictions Volume 18 Issue Part 4 Page 259-271 Year of Publication 2009 Date of Publication July 2009 NEURO 2009 <456> Database EMBASE Accession Number 2009384627 Authors Mysels D. Institution (Mysels) Columbia Presbyterian Medical Center, New York State Psychiatric Institution, Division on Substance Use Research, 1051 Riverside Drive, New York, NY 10032, Country of Publication United Kingdom Title The kappa-opiate receptor impacts the pathophysiology and behavior of substance use. Source American Journal on Addictions. 18(4)(pp 272-276), 2009. Date of Publication: July 2009. Publisher Informa Healthcare Abstract There is increasing evidence that the kappa-opiate receptor, in addition to the mu-opiate receptor, plays an important role in substance use pathophysiology and behavior. As dopamine activity is upregulated through chronic substance use, kappa receptor activity, mediated through the peptide dynorphin, is upregulated in parallel. Dynorphin causes dysphoria and decreased locomotion, and the upregulation of its activity on the kappa receptor likely dampens the excitation caused by increased dopaminergic activity. This feedback mechanism may have significant clinical implications for treating drug dependent patients in various stages of their pathology. ISSN 1055-0496 Publication Type Journal: Article Journal Name American Journal on Addictions Volume 18 Issue Part 4 Page 272-276 Year of Publication 2009 Date of Publication July 2009 NEURO 2009 <476> Database EMBASE Accession Number 2009401701 Authors Lee J.L.C. Institution (Lee) School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom. Country of Publication United Kingdom Title Reconsolidation: maintaining memory relevance. Source Trends in Neurosciences. 32(8)(pp 413-420), 2009. Date of Publication: August 2009. Publisher Elsevier Ltd Abstract The retrieval of a memory places it into a plastic state, the result of which is that the memory can be disrupted or even enhanced by experimental treatment. This phenomenon has been conceptualised within a framework of memories being reactivated and then reconsolidated in repeated rounds of cellular processing. The reconsolidation phase has been seized upon as crucial for the understanding of memory stability and, more recently, as a potential therapeutic target in the treatment of disorders such as post-traumatic stress and drug addiction. However, little is known about the reactivation process, or what might be the adaptive function of retrieval-induced plasticity. Reconsolidation has long been proposed to mediate memory updating, but only recently has this hypothesis been supported experimentally. Here, the adaptive function of memory reconsolidation is explored in more detail, with a strong emphasis on its role in updating memories to maintain their relevance. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 0166-2236 Publication Type Journal: Article Journal Name Trends in Neurosciences Volume 32 Issue Part 8 Page 413-420 Year of Publication 2009 Date of Publication August 2009 NEURO (A) 2009 <485> Database EMBASE Accession Number 2009412426 Authors Wilson D.I.G. MacLaren D.A.A. Winn P. Institution (Wilson, MacLaren, Winn) School of Psychology, University of St Andrews, St Mary's Quad, South Street, St Andrews, Fife KY16 9JP, United Kingdom. Country of Publication United Kingdom Title Bar pressing for food: Differential consequences of lesions to the anterior versus posterior pedunculopontine. Source European Journal of Neuroscience. 30(3)(pp 504-513), 2009. Date of Publication: August 2009. Publisher Blackwell Publishing Ltd Abstract The pedunculopontine tegmental nucleus (PPTg) is in a key position to participate in operant reinforcement via its connections with the corticostriatal architecture and the medial reticular formation. Indeed, previous work has demonstrated that rats bearing lesions of the whole PPTg are impaired when learning to make two bar presses for amphetamine reinforcement. Anterior and posterior portions of the PPTg make different anatomical connections, including preferential projections by the anterior PPTg to substantia nigra pars compacta dopamine neurons and by the posterior PPTg to ventral tegmental area dopamine neurons. We wanted to assess the effects of anterior and posterior PPTg ibotenate lesions on rats learning simple and more complex schedules of natural reinforcement. We trained rats with lesions to the anterior PPTg (n = 11) and the posterior PPTg (n = 5) [and appropriate controls (n = 15)] to bar press for food on a variety of fixed-ratio and variable-ratio reinforcement schedules and then during extinction. We found that posterior PPTg-lesioned rats bar pressed at lower rates, were slower to learn to bar press, and often had deficits characteristic of impaired learning and/or motivation. In contrast, anterior PPTg-lesioned rats learned to bar press for reinforcement at normal rates. However, they made errors of perseveration and anticipation throughout many schedules, and pressed at a higher rate than controls during extinction, deficits best characterized as reflecting disorganized response control. Together, these data suggest that the anterior PPTg and posterior PPTg (and their related circuits) contribute differently to reinforcement learning, incentive motivation, and response control, processes that are considered to malfunction in drug addiction. copyright Federation of European Neuroscience Societies and Blackwell Publishing Ltd. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 30 Issue Part 3 Page 504-513 Year of Publication 2009 Date of Publication August 2009 NEURO 2009 <488> Database EMBASE Accession Number 2009376748 Authors Kalivas P.W. Institution (Kalivas) Department of Neurosciences, Medical University of South Carolina, Ashley Avenue, BSB 410, Charleston, SC 29425, United States. Country of Publication United Kingdom Title The glutamate homeostasis hypothesis of addiction. Source Nature Reviews Neuroscience. 10(8)(pp 561-572), 2009. Date of Publication: August 2009. Publisher Nature Publishing Group Abstract Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drugseeking behaviours can be linked to an enduring imbalance between synaptic and nonsynaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction. copyright 2009 Macmillan Publishers Limited. All rights reserved. ISSN 1471-003X Publication Type Journal: Review Journal Name Nature Reviews Neuroscience Volume 10 Issue Part 8 Page 561-572 Year of Publication 2009 Date of Publication August 2009 NEURO (A) 2009 <496> Database EMBASE Accession Number 2009389909 Authors Sorensen G. Wegener G. Hasselstrom J. Hansen T.V.O. Wortwein G. Fink-Jensen A. Woldbye D.P.D. Institution (Sorensen, Wortwein, Fink-Jensen, Woldbye) Laboratory of Neuropsychiatry, Copenhagen Mental Health Center Rigshospitalet, Copenhagen, Denmark. (Sorensen, Wortwein, Fink-Jensen, Woldbye) Department of Neuroscience and Pharmacology, University of Copenhagen, 9 Blegdamsvej, Copenhagen DK-2100, Denmark. (Wegener, Hasselstrom) Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. (Hansen) Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. (Woldbye) Laboratory of Neuropsychiatry, Rigshospitalet University Hospital, Copenhagen DK-2100, Denmark. Country of Publication United Kingdom Title Neuropeptide Y infusion into the shell region of the rat nucleus accumbens increases extracellular levels of dopamine. Source NeuroReport. 20(11)(pp 1023-1026), 2009. Date of Publication: 15 Jul 2009. Publisher Lippincott Williams and Wilkins Abstract Increases in extracellular dopamine in the shell region of the nucleus accumbens are centrally involved in mediating reinforcement of addictive drugs. Neuropeptide Y (NPY) and its receptors are present in the nucleus accumbens and have been implicated in addiction mechanisms. This study further explored the potential role of NPY in addiction mechanisms using microdialysis to measure extracellular dopamine in vivo after infusion of NPY directly into the accumbal shell region of adult rats. NPY was found to dose-dependently increase extracellular dopamine levels, indicating that NPY could play an important role in drug reinforcement by modulating accumbal dopamine levels. copyright 2009 Lippincott Williams & Wilkins, Inc. ISSN 0959-4965 Publication Type Journal: Article Journal Name NeuroReport Volume 20 Issue Part 11 Page 1023-1026 Year of Publication 2009 Date of Publication 15 Jul 2009 NEURO 2009 <499> Database EMBASE Accession Number 2009430248 Authors Gubellini P. Salin P. Kerkerian-Le Goff L. Baunez C. Institution (Gubellini, Salin, Kerkerian-Le Goff) Institut de Biologie du Developpement de Marseille-Luminy (IBDML), UMR6216 CNRS/Universite de la Mediterranee, Case 907, Parc Scientifique Luminy, 13288 Marseille Cedex 9, France. (Baunez) Laboratoire de Neurobiologie de la Cognition (LNC), UMR6155 CNRS, Marseille, France. Country of Publication United Kingdom Title Deep brain stimulation in neurological diseases and experimental models: From molecule to complex behavior. Source Progress in Neurobiology. 89(1)(pp 79-123), 2009. Date of Publication: September 2009. Publisher Elsevier Ltd Abstract Deep brain stimulation (DBS) has proven to be capable of providing significant benefits for several neuropathologies. It is highly effective in reducing the motor symptoms of Parkinson's disease, essential tremor, and dystonia, and in alleviating chronic pain. Recently, also Tourette syndrome, obsessive-compulsive disorder and treatment-resistant depression have been treated by DBS with encouraging results. However, despite these clinical achievements, the precise action mechanisms of DBS still need to be fully characterized. For this reason, several animal models of DBS have been developed, bringing new insights on the effects of this treatment at molecular and cellular level, and providing new evidence on its physiological and behavioral consequences. In parallel, physiological and imaging studies in patients have contributed to better understanding DBS impact on the function of brain circuits. Here we review the clinical data and experimental work in vitro, ex vivo and in vivo (mostly arisen from studies on DBS of the subthalamic nucleus) in the treatment of PD, which led to the actual knowledge of DBS mechanisms, from molecular to complex behavioral levels. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 0301-0082 Publication Type Journal: Review Journal Name Progress in Neurobiology Volume 89 Issue Part 1 Page 79-123 Year of Publication 2009 Date of Publication September 2009 NEURO 2009 <509> Database EMBASE Accession Number 2009452934 Authors Sun X. Wolf M.E. Institution (Sun, Wolf) Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, United States. Country of Publication United Kingdom Title Nucleus accumbens neurons exhibit synaptic scaling that is occluded by repeated dopamine pre-exposure. Source European Journal of Neuroscience. 30(4)(pp 539-550), 2009. Date of Publication: August 2009. Publisher Blackwell Publishing Ltd Abstract Synaptic scaling has been proposed as a form of plasticity that may contribute to drug addiction but it has not been previously demonstrated in the nucleus accumbens (NAc), a critical region for addiction. Here we demonstrate bidirectional synaptic scaling in postnatal rat NAc neurons that were co-cultured with prefrontal cortical neurons to restore excitatory input. Prolonged activity blockade (1-3 days) with an AMPA receptor antagonist increased cell surface (synaptic and extrasynaptic) glutamate receptor 1 (GluR1) and GluR2 but not GluR3, as well as GluR1/2 co-localization on the cell surface and total GluR1 and GluR2 protein levels. A prolonged increase in activity (bicuculline, 48 h) produced opposite effects. These results suggest that GluR1/2-containing AMPA receptors undergo synaptic scaling in NAc neurons. GluR1 and GluR2 surface expression was also increased by tetrodotoxin alone or in combination with an N-methyl-d-aspartate receptor or AMPA receptor antagonist but not by the l-type Ca2+ channel antagonist nifedipine. A cobalt-quenching assay confirmed the immunocytochemical results indicating that synaptic scaling after activity blockade did not involve a change in abundance of GluR2-lacking AMPA receptors. Increased AMPA receptor surface expression after activity blockade required protein synthesis and was occluded by inhibition of the ubiquitin-proteasome system. Repeated dopamine (DA) treatment, which leads to upregulation of surface GluR1 and GluR2, occluded activity blockade-induced synaptic scaling. These latter results indicate an interaction between cellular mechanisms involved in synaptic scaling and adaptive mechanisms triggered by repeated DA receptor stimulation, suggesting that synaptic scaling may not function normally after exposure to DAreleasing drugs such as cocaine. copyright 2009 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 30 Issue Part 4 Page 539-550 Year of Publication 2009 Date of Publication August 2009 NEURO 2009 <522> Database EMBASE Accession Number 2009429236 Authors Uhl G.R. Drgon T. Johnson C. Liu Q.-R. Institution (Uhl, Drgon, Johnson, Liu) Molecular Neurobiology Branch, NIH-IRP (NIDA), Box 5180, Baltimore, MD 21224, United States. Country of Publication United Kingdom Title Addiction genetics and pleiotropic effects of common haplotypes that make polygenic contributions to vulnerability to substance dependence. Source Journal of Neurogenetics. 23(3)(pp 272-282), 2009. Date of Publication: January 2009. Publisher Informa Healthcare Abstract Abundant evidence from family, adoption, and twin studies point to large genetic contributions to individual differences in vulnerability to develop dependence on one or more addictive substances. Twin data suggest that most of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances. Molecular genetic studies, especially genomewide and candidate gene association studies, have elucidated common haplotypes in dozens of genes that appear to make polygenic contributions to vulnerability to developing dependence. Most genes that harbor currently identified addictionassociated haplotypes are expressed in the brain. Haplotypes in many of the same genes are identified in genomewide association studies that compare allele frequencies in substance dependent vs. control individuals from European, African, and Asian racial/ethnic backgrounds. Many of these addiction-associated haplotypes display pleiotropic influences on a variety of related brain-based phenotypes that display 1) substantial heritability and 2) clinical cooccurence with substance dependence. Copyright copyright 2009 Informa UK Ltd. ISSN 0167-7063 Publication Type Journal: Review Journal Name Journal of Neurogenetics Volume 23 Issue Part 3 Page 272-282 Year of Publication 2009 Date of Publication January 2009 NEURO (A) 2009 <540> Database EMBASE Accession Number 2009481208 Authors Cifani C. Zanoncelli A. Tessari M. Righetti C. Di Francesco C. Ciccocioppo R. Massi M. Melotto S. Institution (Cifani, Ciccocioppo, Massi) Department of Experimental Medicine and Public Health, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy. (Zanoncelli, Tessari, Righetti, Di Francesco, Melotto) Department of Biology, Neurosciences CEDD, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. Country of Publication United Kingdom Title Pre-exposure to environmental cues predictive of food availability elicits hypothalamic-pituitary-adrenal axis activation and increases operant responding for food in female rats. Source Addiction Biology. 14(4)(pp 397-407), 2009. Date of Publication: October 2009. Publisher Blackwell Publishing Ltd Abstract The present study was undertaken to develop an animal model exploiting food cue-induced increased motivation to obtain food under operant self-administration conditions. To demonstrate the predictive validity of the model, rimonabant, fluoxetine, sibutramine and topiramate, administered 1 hour before the experiment, were tested. For 5 days, female Wistar rats were trained to self-administer standard 45 mg food pellets in one daily session (30 minutes) under FR1 (fixed ratio 1) schedule of reinforcement. Rats were then trained to an FR3 schedule and finally divided into two groups. The first group (control) was subjected to a standard 30 minutes FR3 food self-administration session. The second group was exposed to five presentations of levers and light for 10 seconds each (every 3 minutes in 15 minutes total). At the completion of this pre-session phase, a normal 30-minute session (as in the control group) started. Results showed that pre-exposure to environmental stimuli associated to food deliveries increased response for food when the session started. Corticosterone and adrenocorticotropic hormone plasma levels, measured after the 15-minute pre-exposure, were also significantly increased. No changes were observed for the other measured hormones (growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, insulin, amylin, gastric inhibitor polypeptide, ghrelin, leptin, peptide YY and pancreatic polypeptide). Rimonabant, sibutramine and fluoxetine significantly reduced food intake in both animals pre-exposed and in those not pre-exposed to food-associated cues. Topiramate selectively reduced feeding only in pre-exposed rats. The present study describes the development of a new animal model to investigate cue-induced increased motivation to obtain food. This model shows face and predictive validity, thus, supporting its usefulness in the investigation of new potential treatments of binge-related eating disorders. In addition, the present findings confirm that topiramate may represent an important pharmacotherapeutic approach to binge-related eating. copyright 2009 Society for the Study of Addiction. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 14 Issue Part 4 Page 397-407 Year of Publication 2009 Date of Publication October 2009 NEURO 2009 <557> Database EMBASE Accession Number 2009430469 Authors Navarro H.A. Howard J.L. Pollard G.T. Carroll F.I. Institution (Navarro) Research Triangle Institute, Post Office Box 12194, Research Triangle Park, NC 27709-2194, United States. (Navarro, Carroll) RTI International, Research Triangle Park, NC, United States. (Howard, Pollard) Howard Associates, LLC, Research Triangle Park, NC, United States. Country of Publication United Kingdom Title Positive allosteric modulation of the human cannabinoid (CB1) receptor by RTI-371, a selective inhibitor of the dopamine transporter. Source British Journal of Pharmacology. 156(7)(pp 1178-1184), 2009. Date of Publication: April 2009. Publisher Nature Publishing Group Abstract Background and purpose: In our search for an indirect dopamine agonist as therapy for cocaine addiction, several selective inhibitors of the dopamine transporter (DAT), which are 3phenyltropane analogues, were assayed for their effect on locomotor activity in mice. Interestingly, several of the compounds showed a poor correlation between stimulation of locomotion and DAT inhibition. One of the compounds, 3beta-(4-methylphenyl)-2beta-[3-(4chlorophenyl) isoxazol-5-yl]tropane (RTI-371), was shown to cross the blood-brain barrier, by binding studies in vivo, and block cocaine-induced locomotor stimulation. As poor pharmacokinetics could not explain the behavioural effects of RTI-371, this compound was screened through our functional assays for activity at other CNS receptors. Initial screening identified RTI-371 as a positive allosteric modulator of the human CB1 (hCB1) receptor. Experimental approach: The effect of RTI-371 and other DAT-selective inhibitors on CP55940-stimulated calcium mobilization was characterized in a calcium mobilization-based functional assay for the hCB1 receptor. Selected compounds were also characterized in a similar assay for human mu opioid receptor activation to assess the specificity of their effects. Key results: RTI-371 and several other DAT-selective inhibitors with atypical actions on locomotor behaviour increased the efficacy of CP55940 in a concentration- dependent manner. Conclusions and implications: These results suggest that the lack of correlation between the DAT-binding affinity and locomotor stimulation of RTI-371 could be due at least in part to its activity as a positive modulator of the hCB1 receptor. copyright 2009 The British Pharmacological Society. ISSN 0007-1188 Publication Type Journal: Article Journal Name British Journal of Pharmacology Volume 156 Issue Part 7 Page 1178-1184 Year of Publication 2009 Date of Publication April 2009 NEURO 2009 <558> Database EMBASE Accession Number 2009468251 Authors Huang W. Li M.D. Institution (Huang, Li) Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Section of Neurobiology, 1670 Discovery Drive, Charlottesville, VA 22911, United States. Country of Publication United Kingdom Title Nicotine modulates expression of miR-140, which targets the 3-untranslated region of dynamin 1 gene (Dnm1). Source International Journal of Neuropsychopharmacology. 12(4)(pp 537-546), 2009. Date of Publication: May 2009. Publisher Cambridge University Press Abstract Nicotine stimulation regulates expression of a diversity of genes, but the underlying mechanisms are largely unknown. MicroRNAs (miRNAs) are short endogenous RNAs known to post-transcriptionally regulate gene expression. To test our hypothesis that miRNAs could mediate nicotine's effect on gene expression regulation, we profiled miRNA expression to explore to what extent miRNAs are modulated by nicotine. Using a rodent miRNA microarray and rat PC12 cell model, we revealed that nicotine selectively modulates expression of multiple miRNAs, indicating that the miRNA pathway is one of cellular mechanisms involved in gene expression regulated by nicotine. Specifically, we demonstrated that nicotine increases expression of miR-140, coordinated with the nicotine-augmented expression of its host gene WWP2. Further, we demonstrated that miR-140* targets the 3-untranslated region of dynamin 1 gene (Dnm1), by direct base-pairing. This targeting represses gene translation in the luciferase reporter assay and induces messenger RNA degradation in Dnm1 expression analysis. Consequently, our data indicate that nicotine regulates Dnm1 expression via the miRNA pathway. Because dynamin 1 has an essential role in synaptic endocytosis in the central nervous system, nicotine-induced miRNA-mediated dynamin 1 expression regulation may illustrate its importance in neural plasticity, which underlies a molecular mechanism of nicotine addiction. Copyright copyright 2009 CINP. ISSN 1461-1457 Publication Type Journal: Article Journal Name International Journal of Neuropsychopharmacology Volume 12 Issue Part 4 Page 537-546 Year of Publication 2009 Date of Publication May 2009 NEURO 2009 <567> Database EMBASE Accession Number 2009476360 Authors Taly A. Corringer P.-J. Guedin D. Lestage P. Changeux J.-P. Institution (Taly) Laboratoire de Chimie Biophysique, Institut de Science et d'Ingenierie Supramoleculaires, UMR 7006 (CNRSUniversite de Strasbourg), 8 Allee Gaspard Monge, 67000 Strasbourg, France. (Corringer) Channel Receptors, CNRS URA 2182, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France. (Guedin, Lestage) Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France. (Changeux) CNRS URA 2182, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France. Country of Publication United Kingdom Title Nicotinic receptors: Allosteric transitions and therapeutic targets in the nervous system. Source Nature Reviews Drug Discovery. 8(9)(pp 733-750), 2009. Date of Publication: 2009. Publisher Nature Publishing Group Abstract Nicotinic receptors - a family of ligand-gated ion channels that mediate the effects of the neurotransmitter acetylcholine - are among the most well understood allosteric membrane proteins from a structural and functional perspective. There is also considerable interest in modulating nicotinic receptors to treat nervous-system disorders such as Alzheimer's disease, schizophrenia, depression, attention deficit hyperactivity disorder and tobacco addiction. This article describes both recent advances in our understanding of the assembly, activity and conformational transitions of nicotinic receptors, as well as developments in the therapeutic application of nicotinic receptor ligands, with the aim of aiding novel drug discovery by bridging the gap between these two rapidly developing fields. ISSN 1474-1776 Publication Type Journal: Review Journal Name Nature Reviews Drug Discovery Volume 8 Issue Part 9 Page 733-750 Year of Publication 2009 Date of Publication 2009 NEURO 2009 <579> Database EMBASE Accession Number 2009497853 Authors Wise R.A. Institution (Wise) Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, United States. Country of Publication United Kingdom Title Roles for nigrostriatal-not just mesocorticolimbic-dopamine in reward and addiction. Source Trends in Neurosciences. 32(10)(pp 517-524), 2009. Date of Publication: October 2009. Publisher Elsevier Ltd Abstract Forebrain dopamine circuitry has traditionally been studied by two largely independent specialist groups: students of Parkinson's disease who study the nigrostriatal dopamine system that originates in the substantia nigra (SN), and students of motivation and addiction who study the role of the mesolimbic and mesocortical dopamine systems that originate in the ventral tegmental area (VTA). The anatomical evidence for independent nigrostriatal and mesolimbic dopamine systems has, however, long been obsolete. There is now compelling evidence that both nominal "systems" participate in reward function and addiction. Electrical stimulation of both SN and VTA is rewarding, blockade of glutamatergic or cholinergic input to either SN or VTA attenuates the habit-forming effects of intravenous cocaine, and dopamine in both nigrostriatal and mesocorticolimbic terminal fields participates in the defining property of rewarding events: the reinforcement of memory consolidation. Thus, the similarities between nigrostriatal and mesolimbic dopamine systems can be as important as their differences. ISSN 0166-2236 Publication Type Journal: Article Journal Name Trends in Neurosciences Volume 32 Issue Part 10 Page 517-524 Year of Publication 2009 Date of Publication October 2009 NEURO (A) 2009 <582> Database EMBASE Accession Number 2009441353 Authors Dracheva S. Lyddon R. Barley K. Marcus S.M. Hurd Y.L. Byne W.M. Institution (Dracheva, Hurd, Byne) James J Peters Veterans Affairs Medical Center, Bronx, NY, United States. (Dracheva, Lyddon, Barley, Marcus, Hurd, Byne) Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States. (Dracheva) Psychiatry Research (4F-02), Bronx VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, United States. Country of Publication United Kingdom Title Editing of serotonin 2C receptor mRNA in the prefrontal cortex characterizes highnovelty locomotor response behavioral trait. Source Neuropsychopharmacology. 34(10)(pp 2237-2251), 2009. Date of Publication: September 2009. Publisher Nature Publishing Group Abstract Serotonin 2C receptor (5-HT2CR) exerts a major inhibitory influence on dopamine (DA) neurotransmission within the mesocorticolimbic DA pathway that is implicated in drug reward and goal-directed behaviors. 5-HT 2CR pre-mRNA undergoes adenosine-to-inosine editing, generating numerous receptor isoforms in brain. As editing influences 5-HT2CR activity, individual differences in editing might influence dopaminergic function and, thereby, contribute to interindividual vulnerability to drug addiction. Liability to drug-related behaviors in rats can be predicted by their level of motor activity in response to a novel environment. Rats with a high locomotor response (high responders; HRs) exhibit enhanced acquisition and maintenance of drug self-administration compared to rats with a low response (low responders; LRs). We here examined 5-HT2CR mRNA editing and expression in HR and LR phenotypes to investigate the relationship between 5-HT2CR function and behavioral traits relevant to drug addiction vulnerability. Three regions of the mesocorticolimbic circuitry (ventral tegmental area (VTA), nucleus accumbens (NuAc) shell, and medial prefrontal cortex (PFC)) were examined. 5-HT2CR mRNA expression and editing were significantly higher in the NuAc shell compared with both the PFC and VTA, implying significant differences in function (including constitutive activity) among 5-HT2CR neuronal populations within the circuitry. The regional differences in editing could, at least in part, arise from the variations in expression levels of the editing enzyme, ADAR2, and/or from the variations in the ADAR2/ADAR1 ratio observed in the study. No differences in the 5-HT 2CR expression were detected between the behavioral phenotypes. However, editing was higher in the PFC of HRs vs LRs, implicating this region in the pathophysiology of drug abuse liability. copyright 2009 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 34 Issue Part 10 Page 2237-2251 Year of Publication 2009 Date of Publication September 2009 NEURO 2009 <603> Database EMBASE Accession Number 2009525060 Authors Fenu S. Wardas J. Morelli M. Institution (Fenu, Morelli) Department of Toxicology, National Institute of Neuroscience, University of Cagliari, Cagliari, Italy. (Morelli) CNR Institute of Neuroscience, Section of Cagliari, Cagliari, Italy. (Wardas) Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. (Morelli) Dipartimento di Tossicologia, Via Ospedale 72, 09124 Cagliari, Italy. Country of Publication United Kingdom Title Impulse control disorders and dopamine dysregulation syndrome associated with dopamine agonist therapy in Parkinson's disease. Source Behavioural Pharmacology. 20(5-6)(pp 363-379), 2009. Date of Publication: September 2009. Publisher Lippincott Williams and Wilkins Abstract Over the last decade, evidence has emerged linking disorders in the impulsive-compulsive spectrum in Parkinson's disease to dopamine receptor agonist treatment. These disorders include hypersexuality, gambling and, to a minor extent, compulsive shopping and eating, as well as dopamine dysregulation syndrome, characterized by an addictive pattern toward dopamine replacement therapy and stereotyped behaviors, such as punding. These syndromes, which have only recently been recognized and are still underdiagnosed, have deleterious social consequences that warrant interventions at the clinical level and promotion of research at the preclinical level. In this review, we first provide a summary of features of Parkinson's disease and current pharmacological therapies associated with the development of dopamine dysregulation syndrome and impulsive-compulsive disorders. We also examine the dopamine receptors and brain areas important in reward and compulsive behaviors. We then critically examine the neuroadaptations in dopaminergic circuitries and the literature concerning gambling, hypersexuality, and other addictive behaviors in parkinsonian patients. Finally, we focus on suggestions pointing to a role for dopamine D3 receptors and sensitization phenomena as the main factors which may be the origin of these disorders. copyright 2009 Wolters Kluwer Health |Lippincott Williams & Wilkins. ISSN 0955-8810 Publication Type Journal: Review Journal Name Behavioural Pharmacology Volume 20 Issue Part 5-6 Page 363-379 Year of Publication 2009 Date of Publication September 2009 NEURO 2009 <605> Database EMBASE Accession Number 2009470873 Authors Goldstein R.Z. Craig A.D.(B.) Bechara A. Garavan H. Childress A.R. Paulus M.P. Volkow N.D. Institution (Goldstein) Center for Translational Neuroimaging, Medical Research, Brookhaven National Laboratory, 30 Bell Ave., Bldg. 490, Upton, NY 11973-5000, United States. (Craig) Atkinson Research Laboratory, Barrow Neurological Institute, Phoenix, AZ 85013, United States. (Bechara) Department of Psychology, University of Southern California, Los Angeles, CA 90089-1061, United States. (Garavan) School of Psychology, Institute of Neuroscience, Trinity College, Dublin, 2, Ireland. (Garavan) Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, United States. (Childress) Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States. (Paulus) Department of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San Diego, 8950 Villa La Jolla Dr., Suite C213, La Jolla, CA 92037-0985, United States. (Volkow) National Institute on Drug Abuse, Bethesda, MD 20892, United States. Country of Publication United Kingdom Title The Neurocircuitry of Impaired Insight in Drug Addiction. Source Trends in Cognitive Sciences. 13(9)(pp 372-380), 2009. Date of Publication: September 2009. Publisher Elsevier Ltd Abstract More than 80% of addicted individuals fail to seek treatment, which might reflect impairments in recognition of severity of disorder. Considered by some as intentional deception, such 'denial' might instead reflect dysfunction of brain networks subserving insight and self-awareness. Here we review the scant literature on insight in addiction and integrate this perspective with the role of: (i) the insula in interoception, self-awareness and drug craving; (ii) the anterior cingulate in behavioral monitoring and response selection (relevant to disadvantageous choices in addiction); (iii) the dorsal striatum in automatic habit formation; and (iv) drug-related stimuli that predict emotional behavior in addicted individuals, even without conscious awareness. We discuss implications for clinical treatment including the design of interventions to improve insight into illness severity in addiction. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 1364-6613 Publication Type Journal: Article Journal Name Trends in Cognitive Sciences Volume 13 Issue Part 9 Page 372-380 Year of Publication 2009 Date of Publication September 2009 NEURO (A) 2009 <630> Database EMBASE Accession Number 2009525085 Authors Ward S.J. Walker E.A. Institution (Ward, Walker) Department of Pharmaceutical Sciences, Temple University, School of Pharmacy, Philadelphia, PA, United States. (Ward) Temple University, School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, United States. Country of Publication United Kingdom Title Sex and cannabinoid CB1 genotype differentiate palatable food and cocaine selfadministration behaviors in mice. Source Behavioural Pharmacology. 20(7)(pp 605-613), 2009. Date of Publication: October 2009. Publisher Lippincott Williams and Wilkins Abstract Both cannabinoid CB1 receptor knockout and antagonism produce well-established attenuation of palatable food and drug self-administration behavior. Although cannabinoid drugs have received attention as pharmacotherapeutics for various disorders, including obesity and addiction, it is unclear whether these agents produce equivalent behavioral effects in females and males. In this study, acquisition of 32% corn oil or 10% Ensure selfadministration, and maintenance of corn oil, Ensure, or 0.56 mg/kg/infusion cocaine selfadministration under both fixed ratio (FR)-1 and progressive ratio (PR) schedule of reinforcement, was compared in male and female wild type (WT) and CB1 knockout (KO) mice. Furthermore, the effect of pretreatment with the CB1 antagonist SR141716 (0.3-3.0) on Ensure self-administration in male and female WT and CB1 KO mice was assessed. CB1 genotype and sex significantly interacted to produce an attenuation of acquisition and maintenance of Ensure self-administration and PR self-administration for both Ensure and cocaine in male CB1 KO mice. In contrast, male CB1 KO mice showed no deficit in acquisition and maintenance of FR-1 responding or in PR responding maintained by corn oil. Sex differences also arose within genotypes for responding maintained under all three reinforcers. Lastly, pretreatment with SR141716 attenuated Ensure self-administration in WT and CB1 KO mice but was approximately five-fold more potent in WT mice than in CB1 KOs. The present data add to a small but growing literature suggesting that the cannabinoid system may be differentially sensitive in its modulation of appetitive behavior in males versus females. copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. ISSN 0955-8810 Publication Type Journal: Article Journal Name Behavioural Pharmacology Volume 20 Issue Part 7 Page 605-613 Year of Publication 2009 Date of Publication October 2009 NEURO (A) 2010 <640> Database EMBASE Accession Number 2009551999 Authors Eagle D.M. Baunez C. Institution (Eagle) Department of Experimental Psychology, University of Cambridge, Downing Site, Cambridge, CB2 3EB, United Kingdom. (Baunez) Laboratory of Neurobiology of Cognition, CNRS UMR6155, Aix-Marseille Universite, Marseille, France. Country of Publication United Kingdom Title Is there an inhibitory-response-control system in the rat? Evidence from anatomical and pharmacological studies of behavioral inhibition. Source Neuroscience and Biobehavioral Reviews. 34(1)(pp 50-72), 2010. Date of Publication: January 2010. Publisher Elsevier Ltd Abstract Many common psychiatric conditions, such as attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), Parkinson's disease, addiction and pathological gambling are linked by a failure in the mechanisms that control, or inhibit, inappropriate behavior. Models of rat behavioral inhibition permit us to study in detail the anatomical and pharmacological bases of inhibitory failure, using methods that translate directly with patient assessment in the clinic. This review updates current ideas relating to behavioral inhibition based on two significant lines of evidence from rat studies:. (1) To integrate new findings from the stop-signal task into existing models of behavioral inhibition, in particular relating to 'impulsive action' control. The stop-signal task has been used for a number of years to evaluate psychiatric conditions and has recently been translated for use in the rat, bringing a wealth of new information to behavioral inhibition research. (2) To consider the importance of the subthalamic nucleus (STN) in the neural circuitry of behavioral inhibition. This function of this nucleus is central to a number of 'disinhibitory' disorders such as Parkinson's disease and OCD, and their therapies, but its role in behavioral inhibition is still undervalued, and often not considered in preclinical models of behavioral control. Integration of these findings has pinpointed the orbitofrontal cortex (OF), dorsomedial striatum (DMStr) and STN within a network that normally inhibits many forms of behavior, including both impulsive and compulsive forms. However, there are distinct differences between behavioral subtypes in their neurochemical modulation. This review brings new light to the classical view of the mechanisms that inhibit behavior, in particular suggesting a far more prominent role for the STN, a structure that is usually omitted from conventional behavioralinhibition networks. The OF-DMStr-STN circuitry may form the basis of a control network that defines behavioral inhibition and that acts to suppress or countermand many forms of inappropriate or maladaptive behavior. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 0149-7634 Publication Type Journal: Review Journal Name Neuroscience and Biobehavioral Reviews Volume 34 Issue Part 1 Page 50-72 Year of Publication 2010 Date of Publication January 2010 NEURO 2009 <660> Database EMBASE Accession Number 2009587489 Authors Sanchis-Segura C. Lopez-Atalaya J.P. Barco A. Institution (Sanchis-Segura) Area de Psicobiologia, Universitat Jaume i, Castello, Spain. (Lopez-Atalaya, Barco) Department of Molecular Neurobiology, Instituto de Neurociencias de Alicante, Universidad Miguel Hernandez-Consejo Superior de Investigaciones Cientificas, Sant Joan, d'Alacant, Alicante, Spain. (Barco) Area de Psicobiologia, Universitat Jaume i, Castello 12071, Spain. Country of Publication United Kingdom Title Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition. Source Neuropsychopharmacology. 34(13)(pp 2642-2654), 2009. Date of Publication: December 2009. Publisher Nature Publishing Group Abstract Histone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Earlier studies have shown that a reduction in histone deacetylase (HDAC) activity results in the enhancement of some psychostimulant-induced behaviors. In this study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant to addictive behavior. Our results support a specific function for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, longlasting, drug-induced behavioral plasticity. copyright 2009 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 34 Issue Part 13 Page 2642-2654 Year of Publication 2009 Date of Publication December 2009 NEURO 2009 <662> Database EMBASE Accession Number 2009586598 Authors Loos M. Van Der Sluis S. Bochdanovits Z. Van Zutphen I.J. Pattij T. Stiedl O. Smit A.B. Spijker S. Institution (Loos, Van Zutphen, Smit, Spijker) Department of Molecular and Cellular Neurobiology, VU University, De Boelelaan 1085, 1081 HV Amsterdam, Netherlands. (Van Der Sluis, Spijker) Departments of Functional Genomics, VU University, Neuroscience Campus Amsterdam, Amsterdam, Netherlands. (Bochdanovits) Departments of Medical Genomics, VU University, Neuroscience Campus Amsterdam, Amsterdam, Netherlands. (Pattij) Departments of Anatomy and Neurosciences, VU University, Neuroscience Campus Amsterdam, Amsterdam, Netherlands. (Stiedl) Behavioral and Cognitive Neuroscience Group, VU University, Neuroscience Campus Amsterdam, Amsterdam, Netherlands. Country of Publication United Kingdom Title Activity and impulsive action are controlled by different genetic and environmental factors. Source Genes, Brain and Behavior. 8(8)(pp 817-828), 2009. Date of Publication: November 2009. Publisher Blackwell Publishing Ltd Abstract Both impulsivity in operant tasks and locomotor activity in a novel open field are known to predict the development of addiction-related behavior in rodents. In this study, we investigated to what extent impulsivity in the five-choice serial reaction time task and various measures of novelty exploration are controlled by shared genetic and environmental factors in 12 different inbred mouse strains. No genetic correlation was observed between the level of impulsivity and levels of activity, a low correlation was observed with traditional measures of anxiety-like behavior (impulsive strains tend to be less anxious) and a highly significant correlation was found between impulsivity and specific aspects of movement. Furthermore, we found that impulsivity and all measures of novelty exploration were under control of different environmental factors. Interestingly, in the dorsal medial prefrontal cortex, a brain region involved in impulsivity and activity in novelty exploration tests; these behavioral measures correlated with the expression of different genes (respectively, Frzb, Snx5, BC056474 and the previously identified Glo1). Taken together, our study shows that impulsivity and activity in novelty exploration tests are genetically and environmentally distinct, suggesting that mouse models of these behaviors provide complementary insights into the development of substance abuse disorder. copyright 2009 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society. ISSN 1601-1848 Publication Type Journal: Article Journal Name Genes, Brain and Behavior Volume 8 Issue Part 8 Page 817-828 Year of Publication 2009 Date of Publication November 2009 NEURO 2009 <757> Database EMBASE Accession Number 2009596318 Authors Bird M.K. Lawrence A.J. Institution (Bird, Lawrence) Florey Neuroscience Institutes, University of Melbourne, Parkville, Vic. 3010, Australia. (Bird, Lawrence) Centre for Neuroscience, University of Melbourne, Parkville, Vic. 3010, Australia. Country of Publication United Kingdom Title The promiscuous mGlu5 receptor - a range of partners for therapeutic possibilities?. Source Trends in Pharmacological Sciences. 30(12)(pp 617-623), 2009. Date of Publication: December 2009. Publisher Elsevier Ltd Abstract The issue of non-specific effects for potential therapeutics is particularly salient in neurological/psychiatric disorders, where adverse drug reactions could impair critical brain functions. The issue of specificity is not limited to candidate molecules, as receptor targets themselves often influence physiological as well as pathological outcomes. Metabotropic glutamate receptor 5 (mGlu5) is an example of a "promiscuous" receptor target that has been implicated in addiction, but also many other processes. However, if receptor modulation could be restricted to specific pathways/brain regions, mGlu5 may still prove to be a viable therapeutic target for various indications. Using this premise, a number of possible methods to refine drug development strategy are discussed, including exploiting specific interactions of mGlu5 with other receptors to narrow the influence of pharmacological agents, and also the use of RNA interference targeted to specific cells/regions of the brain. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 0165-6147 Publication Type Journal: Article Journal Name Trends in Pharmacological Sciences Volume 30 Issue Part 12 Page 617-623 Year of Publication 2009 Date of Publication December 2009 NEURO 2009 <775> Database EMBASE Accession Number 2009093813 Authors Long Q. Zhang Q. Ott J. Institution (Long, Zhang, Ott) Beijing Institute of Genomics, Chinese Academy of Sciences, No. 7 Bei Tu Cheng West Road, Beijing 100029, China. (Long) Wellcome Trust Sanger Institute, Cambridge, United Kingdom. Country of Publication United Kingdom Title Detecting disease-associated genotype patterns. Source BMC Bioinformatics. 10(SUPPL. 1), 2009. Article Number: S75. Date of Publication: 30 Jan 2009. Publisher BioMed Central Ltd. Abstract Background: In addition to single-locus (main) effects of disease variants, there is a growing consensus that gene-gene and gene-environment interactions may play important roles in disease etiology. However, for the very large numbers of genetic markers currently in use, it has proven difficult to develop suitable and efficient approaches for detecting effects other than main effects due to single variants. Results: We developed a method for jointly detecting disease-causing single-locus effects and gene-gene interactions. Our method is based on finding differences of genotype pattern frequencies between case and control individuals. Those single-nucleotide polymorphism markers with largest single-locus association test statistics are included in a pattern. For a logistic regression model comprising three disease variants exerting main and epistatic interaction effects, we demonstrate that our method is vastly superior to the traditional approach of looking for single-locus effects. In addition, our method is suitable for estimating the number of disease variants in a dataset. We successfully apply our approach to data on Parkinson Disease and heroin addiction. Conclusion: Our approach is suitable and powerful for detecting disease susceptibility variants with potentially small main effects and strong interaction effects. It can be applied to large numbers of genetic markers. copyright 2009 Long et al; licensee BioMed Central Ltd. Publication Type Journal: Conference Paper Journal Name BMC Bioinformatics Volume 10 Issue Part SUPPL. 1 Year of Publication 2009 Date of Publication 30 Jan 2009 NEURO 2009 <861> Database EMBASE Accession Number 0019661838 Authors Bergen S. Chen J. Dagdan E. Foon T.S. Goes F.S. Houlihan L.M. Kloiber S. Kumar R.A. Kuzman M.R. Menke A. Pedroso I. Videtic A. Villafuerte S. DeLisi L.E. Institution (Bergen, Chen, Dagdan, Foon, Goes, Houlihan, Kloiber, Kumar, Kuzman, Menke, Pedroso, Videtic, Villafuerte, DeLisi) Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. Country of Publication United Kingdom Title Selected summaries from the XVI World Congress of Psychiatric Genetics, Osaka, Japan, 11-15 October 2008.. Source Psychiatric genetics. 19(5)(pp 219-236), 2009. Date of Publication: Oct 2009. Abstract The XVI World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics took place in Osaka, Japan, October 2008. Approximately 600 participants gathered to discuss the latest molecular genetic findings relevant to serious mental illnesses, including schizophrenia, bipolar disorder, major depression, alcohol and drug abuse, autism, and attention-deficit disorder. Recently, the field has advanced considerably and includes new genome-wide association studies with the largest numbers of individuals screened and density of markers to date, as well as newly uncovered genetic phenomena, such as copy number variation that may prove to be relevant for specific brain disorders. The following report represents some of the areas covered during this conference and some of the major new findings presented. Publication Type Journal: Conference Paper Journal Name Psychiatric genetics Volume 19 Issue Part 5 Page 219-236 Year of Publication 2009 Date of Publication Oct 2009 NEURO 2009 <862> Database EMBASE Accession Number 0019512960 Authors Doehring A. Kirchhof A. Lotsch J. Institution (Doehring, Kirchhof, Lotsch) Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. Country of Publication United Kingdom Title Genetic diagnostics of functional variants of the human dopamine D2 receptor gene.. Source Psychiatric genetics. 19(5)(pp 259-268), 2009. Date of Publication: Oct 2009. Abstract INTRODUCTION: The importance of dopamine D2 receptors (DRD2) for central nervous dopaminergic signalling makes variants in the DRD2 gene potential modulators of the risk or course of various behavioural, psychiatric or neurologic diseases (e.g. addiction, schizophrenia, Parkinson's disease). We developed Pyrosequencing genetic screening assays for single nucleotide polymorphisms spanning the whole range of the DRD2 gene locus up to the functionally related ankyrin repeat and kinase domain containing 1 gene (ANKK1) located at approximately 10 kb downstream of DRD2. METHODS: Assays for 11 genetic variants with reported functional association were developed in DNA samples from 300 unrelated healthy Caucasians and validated by independent conventional sequencing. RESULTS: In all DNA samples the DRD2/ANKK1 genetic variants were identified correctly as verified by the control samples. The observed frequencies of homozygous, heterozygous and noncarriers of the minor alleles were in agreement with the Hardy-Weinberg equilibrium. Observed minor allele frequencies were DRD2 rs12364283T>C: 6.5%, rs1799978A>G: 4.8%, rs1799732C del: 14.2%, rs4648317C>T: 12.8%, rs1079597G>A: 13.8%, rs1076560G>T: 14.5%, rs1800496C>T: 0.2%, rs1801028C>G: 3.0%, rs6275C>T: 32.7%, rs6277C>T: 53.0% and ANKK1 rs1800497C>T: 17.5%. CONCLUSION: The presently developed Pyrosequencing assays are provided to facilitate further research toward personalized approaches to pathophysiological conditions involving behavioural, psychiatric and neurologic disorders including addiction, schizophrenia and Parkinson's disease. Publication Type Journal: Article Journal Name Psychiatric genetics Volume 19 Issue Part 5 Page 259-268 Year of Publication 2009 Date of Publication Oct 2009 NEURO 2009 <864> Database EMBASE Accession Number 2010003158 Authors Bacher I. Wu B. Shytle D.R. George T.P. Institution (Bacher, Wu, George) University of Toronto, Department of Psychiatry, Faculty of Medicine, Toronto, Canada. (Bacher, Wu, George) Centre for Addiction and Mental Health (CAMH), Schizophrenia Program, 250 College Street, Toronto, ON M5T 1R8, Canada. (Shytle) Department of Psychiatry, Behavioral Sciences and Neurosurgery, Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, FL 33612, United States. Country of Publication United Kingdom Title Mecamylamine a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Source Expert Opinion on Pharmacotherapy. 10(16)(pp 2709-2721), 2009. Date of Publication: 2009. Publisher Informa Healthcare Abstract Mecamylamine (Inversine), the first orally available antihypertensive agent launched in the 1950s, is rarely used today for hypertension because of its widespread ganglionic side effects at antihypertensive doses (25-90 mg/day). However, more recent clinical studies suggest that mecamylamine is effective at much lower doses for blocking the central and peripheral effects of nicotine. Pharmacologically, mecamylamine has been well characterized as a nonselective and noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Because mecamylamine easily crosses the blood brain barrier at relatively low doses (2.5-10 mg), it has been used by several research groups over the past two decades investigating the role of central nAChRs in the etiology and treatment of various neuropsychiatric disorders, including addiction disorders, Tourette's syndrome, schizophrenia and various cognitive and mood disorders. Two independent Phase II clinical trials recently confirmed mecamylamine's hypothesized antidepressant activity and suggest that it may be effective as an augmentation pharmacotherapy for SSRI treatment resistant major depression. These areas of investigation for mecamylamine are reviewed and recommendations for future research directions are proposed. copyright 2009 Informa UK Ltd. ISSN 1465-6566 Publication Type Journal: Review Journal Name Expert Opinion on Pharmacotherapy Volume 10 Issue Part 16 Page 2709-2721 Year of Publication 2009 Date of Publication 2009 NEURO (A) 2009 <898> Database EMBASE Accession Number 2010054924 Authors Biala G. Kruk M. Institution (Biala, Kruk) Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland. Country of Publication United Kingdom Title Effects of co-administration of bupropion and nicotine or D-amphetamine on the elevated plus maze test in mice. Source Journal of Pharmacy and Pharmacology. 61(4)(pp 493-502), 2009. Date of Publication: April 2009. Publisher Pharmaceutical Press Abstract Objectives: A variety of abused drugs, including psychostimulants, can modulate the expression of anxiety. Although the effect of nicotine and D-amphetamine on anxiety-related behaviour in animal models has been investigated, the mechanisms underlying the anxiogenic or anxiolytic actions of these drugs have not been clarified. Bupropion is an antidepressant drug which may alleviate some symptoms of nicotine withdrawal, although its effects on anxiety are not clear. We have investigated the effect of nicotine and Damphetamine on anxiety in the elevated plus maze test in mice. Methods: We examined the influence of acute administration of nicotine (0.1 mg/kg, s.c.) and D-amphetamine (2 mg/kg, i.p.) on anxiety level. We then evaluated the anxiety-related response after subchronic injection of both psychostimulants, including crossover effects. For this purpose, nicotine (0.1 mg/kg, s.c.) was administered daily for six days, and on the seventh day mice were challenged with nicotine (0.1 mg/kg, s.c.) or D-amphetamine (2 mg/ kg, i.p.). A distinct group of mice was pretreated with D-amphetamine (2 mg/kg, i.p., 8 days), and subjected to Damphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.) challenge on the ninth day. Moreover, we investigated acute and subchronic effects of co-administration of bupropion (5, 10 and 20 mg/kg; i.p.) and nicotine or D-amphetamine. Key findings: We observed that acute anxiogenic effects of nicotine and D-amphetamine as well as the development of tolerance and cross-tolerance to their effects were blunted by a pretreatment with a nonactive dose of bupropion (5 mg/kg, i.p.). Conclusions: These results demonstrated that similar neural mechanisms were involved in the regulation of nicotine and D-amphetamine anxiety-like behaviour in mice. The results have provided new findings to support the use of bupropion in the treatment of nicotine and/or amphetamine addiction. copyright 2009 The Authors. ISSN 0022-3573 Publication Type Journal: Article Journal Name Journal of Pharmacy and Pharmacology Volume 61 Issue Part 4 Page 493-502 Year of Publication 2009 Date of Publication April 2009