Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
NEURO <2> Database EMBASE Accession Number 2009290906 Authors Nikolic M. Institution (Nikolic) Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom. Country of Publication United Kingdom Title Unravelling the complex role of Cdk5 in the developing cerebral cortex. Source Future Neurology. 3(6)(pp 729-743), 2008. Date of Publication: 2008. Publisher Future Medicine Ltd. Abstract The normal development of the mammalian CNS is entirely dependent on the coordinated behavior of its cellular components. Particular importance is attributed to the correct morphology, migration and communication of neurons. Recent years have seen the identification of many extracellular, cell surface and intracellular signaling molecules that are important for normal CNS development, consequently triggering huge progress in our understanding of the complex processes involved. A key molecule to emerge is Cdk5. To date, Cdk5 has been functionally linked with controlled neuronal morphology, migration, synaptic function, cognition, drug addiction, neuronal death and neurodegeneration. The complexity of its function has been confirmed by the ever increasing number of diverse upstream regulators, protein substrates and biological consequences of altered catalytic function. The aim of this review is to consolidate recent findings concerning the role of Cdk5 in the developing nervous system, particularly the cerebral cortex, where its importance is most clearly evidenced. copyright 2008 Future Medicine. ISSN 1479-6708 Publication Type Journal: Review Journal Name Future Neurology Volume 3 Issue Part 6 Page 729-743 Year of Publication 2008 Date of Publication 2008 NEURO <16> Database EMBASE Accession Number 2009249808 Authors Nugent F.S. Niehaus J.L. Kauer J.A. Institution (Nugent, Niehaus, Kauer) Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI, United States. (Kauer) Department of Molecular Pharmacology, Physiology and Biotechnology and Neuroscience, Brown University, BioMed Building, 171 Meeting St, Providence, RI 02912, United States. Country of Publication United Kingdom Title PKG and PKA signaling in LTP at GABAergic synapses. Source Neuropsychopharmacology. 34(7)(pp 1829-1842), 2009. Date of Publication: June 2009. Publisher Nature Publishing Group Abstract Drugs of abuse usurp the mechanisms underlying synaptic plasticity in areas of the brain, a process that may contribute to the development of addiction. We previously reported that GABAergic synapses onto dopaminergic neurons in the ventral tegmental area (VTA) exhibit long-term potentiation (LTP(GABA)) blocked by in vivo exposure to morphine. The presynaptically maintained LTP requires the retrogradely released nitric oxide (NO) to activate a presynaptic cGMP signaling cascade. Previous work reported that inhibitory GABA(A) receptor synapses in the VTA are also potentiated by cAMP. Here, we explored the interactions between cGMP-dependent (PKG) and cAMP-dependent (PKA) protein kinases in the regulation of these GABAergic synapses and LTP(GABA). Activation of PKG was required for NO-cGMP signaling and was also essential for the induction of synaptically elicited LTP(GABA), but not for its maintenance. Synapses containing GABA(A) receptors were potentiated by NO-cGMP signaling, whereas synapses containing GABA(B) receptors on the same cells were not potentiated. Moreover, although the cAMP-PKA system potentiated GABA(A) synapses, synaptically induced LTP(GABA) was independent of PKA activation. Surprisingly, however, raising cGMP levels saturated potentiation of these synapses, precluding further potentiation by cAMP and suggesting a convergent end point for both signaling pathways in the regulation of GABAergic release. We further found that persistent GABAergic synaptic modifications observed with in vivo morphine did not involve the presynaptic cAMP-PKA cascade. Taken together, our data suggest a synapse-specific role for NO-cGMP-PKG signaling pathway in opioid-induced plasticity of VTA GABA(A) synapses. copyright 2009 Nature Publishing Group. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 34 Issue Part 7 Page 1829-1842 Year of Publication 2009 Date of Publication June 2009 NEURO (A) <18> Database EMBASE Accession Number 2009249818 Authors Olsen C.M. Winder D.G. Institution (Olsen, Winder) Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States. (Olsen, Winder) Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN, United States. (Olsen, Winder) JF Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, TN, United States. (Winder) Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 724B MRB 1, 23rd and Pierce Avenue S, Nashville, TN 37232-0615, United States. Country of Publication United Kingdom Title Operant sensation seeking engages similar neural substrates to operant drug seeking in C57 mice. Source Neuropsychopharmacology. 34(7)(pp 1685-1694), 2009. Date of Publication: June 2009. Publisher Nature Publishing Group Abstract Novelty and sensation seeking have been associated with elevated drug intake in human and animal studies, suggesting overlap in the circuitry mediating these behaviors. In this study, we found that C57Bl6J mice readily acquired operant responding for dynamic visual stimuli, a phenomenon we term operant sensation seeking (OSS). Like operant studies using other reinforcers, mice responded on fixed and progressive ratio schedules, were resistant to extinction, and had sustained responding with extended access. We also found that OSS, like psychostimulant self-administration, is sensitive to disruption of dopamine signaling. Low doses of the dopamine antagonist cis-flupenthixol increased active lever responding, an effect reported for psychostimulant self-administration. Additionally, D1-deficient mice failed to acquire OSS, although they readily acquired lever pressing for food. Finally, we found that one common measure of novelty seeking, locomotor activity in a novel open field, did not predict OSS performance. OSS may have predictive validity for screening compounds for use in the treatment of drug addiction. In addition, we also discuss the potential relevance of this animal model to the field of behavioral addictions. copyright 2009 Nature Publishing Group. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 34 Issue Part 7 Page 1685-1694 Year of Publication 2009 Date of Publication June 2009 NEURO (A) <22> Database EMBASE Accession Number 2009244761 Authors Prakash S. Ambrosio E. Alguacil L.F. del Olmo N. Institution (Prakash, Alguacil, del Olmo) Departamento de Farmacologia, Tecnologia y Desarrollo Farmaceutico, Facultad de Farmacia, Universidad San Pablo CEU, Boadilla del Monte, 28668 Madrid, Spain. (Ambrosio) Departamento de Psicobiologia, Facultad de Psicologia, UNED, 28040 Madrid, Spain. Country of Publication United Kingdom Title Genetic differences in hippocampal synaptic plasticity. Source Neuroscience. 161(2)(pp 342-346), 2009. Date of Publication: 30 Jun 2009. Publisher Elsevier Ltd Abstract Synaptic plasticity is considered a physiological substrate for learning and memory [Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87-136] that contributes to maladaptive learning in drug addiction [Schoenbaum G, Roesch MR, Stalnaker TA (2006) Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci 29:116-124]. Many studies have revealed that drug addiction has a strong hereditary component [Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69; Uhl GR (2004) Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology 47 (Suppl 1):140147], however the contribution of the genetic background to drug-induced changes in synaptic plasticity has been scarcely studied. The present study reports on an analysis of long-term potentiation (LTP) and depotentiation in Lewis (LEW) and Fischer-344 (F344) rats, two inbred rat strains that show different proneness to drugs of abuse and are considered an experimental model of genetic vulnerability to addiction [Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69]. The induction of saturated-LTP was similar in LEW and F344 rats treated with saline or cocaine. However, only slices from LEW salinetreated rats showed the reversal of LTP; thus, the depotentiation of saturated-LTP was not observed in cocaine-injected LEW rats and in F344 animals (treated either with cocaine or saline). These results suggest significant differences in hippocampal synaptic plasticity between Lewis and Fischer 344 rats. copyright 2009 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 161 Issue Part 2 Page 342-346 Year of Publication 2009 Date of Publication 30 Jun 2009 NEURO <35> Database EMBASE Accession Number 2009219374 Authors Leeman R.F. Grant J.E. Potenza M.N. Institution (Leeman) Yale University School of Medicine, Substance Abuse Center, CMHC, 34 Park Street, New Haven, CT 06519, United States. (Grant) Department of Psychiatry, University of Minnesota Medical Center, St Paul, MN, United States. (Potenza) Department of Psychiatry, Child Study Center, Yale University School of Medicine, New Haven, CT, United States. Country of Publication United Kingdom Title Behavioral and neurological foundations for the moral and legal implications of intoxication, addictive behaviors and disinhibition. Source Behavioral Sciences and the Law. 27(2)(pp 237-259), 2009. Date of Publication: 2009. Publisher John Wiley and Sons Ltd Abstract Disinhibition and addictive behaviors are related and carry moral implications. Both typically involve diminished consideration of negative consequences, which may result in harm to oneself or others. Disinhibition may occur on state and trait levels, and addictive substances may elicit disinhibitory states, particularly when intoxication is reached. Data suggest that trait disinhibition and addictions may be conceptualized as involving misdirected motivation with underlying biological bases including genetic factors, alterations in neurotransmitter systems and differences in regional brain function. The influences of intoxication on the brain share similarities with cognitive impairments in individuals with chronic substance abuse and those with trait disinhibition related to frontal lobe injuries. These findings raise questions about volitional impairment and morality. Although impaired volition related to disinhibition and addictive behaviors has been studied from multiple perspectives, additional research is needed to further characterize mechanisms of impairment. Such findings may have important implications in multiple legal and psychiatric domains. Copyright copyright 2009 John Wiley & Sons, Ltd. ISSN 0735-3936 Publication Type Journal: Article Journal Name Behavioral Sciences and the Law Volume 27 Issue Part 2 Page 237-259 Year of Publication 2009 Date of Publication 2009 NEURO <62> Database EMBASE Accession Number 2009209122 Authors Blum K. Chen A.L.C. Chen T.J. Braverman E.R. Reinking J. Blum S.H. Cassel K. Downs B.W. Waite R.L. Williams L. Prihoda T.J. Kerner M.M. Palomo T. Comings D.E. Tung H. Rhoades P. Oscar-Berman M. Institution (Blum) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, United States. (Chen) Engineering and Management of Advanced Technology, Chang Jung University, Taiwan (Republic of China). (Chen, Reinking) Department of Occupational Health and Safety, Chang Jung University, Taiwan (Republic of China). (Braverman) Department of Neurosurgery, Weill Cornell College of Medicine, New York, NY, United States. (Blum, Blum, Cassel) Department of Psychoneurogenetics, Synaptamine, Inc., San Antonio, TX, United States. (Blum, Downs, Waite, Williams) Deparment of Nutrigenomics, LifeGen, Inc, San Diego, CA, United States. (Prihoda) Department of Pathology, University of Texas Health Science Center, San Antonio, TX, United States. (Blum, Braverman, Kerner) Department of Neurological Research, Path Research Foundation, New York, NY, United States. (Palomo) Hospital Universitario 12 de Octubre, Madrid, Spain. (Comings) Carlsbad Science Foundation, Emeritus, City of Hope National Medical Center, Duarte, CA, United States. (Tung) University of California, San Diego Medical Center, Neurological Surgery (Brain and Spinal Disorders), San Diego, CA, United States. (Rhoades) Central Valley Pain Management and Wellness Modesto, CA, United States. (Oscar-Berman) Boston University School of Medicine and Boston VAMC, Boston, MA, United States. Country of Publication United Kingdom Title Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): A commentary. Source Theoretical Biology and Medical Modelling. 5, 2008. Article Number: 24. Date of Publication: 2008. Publisher BioMed Central Ltd. Abstract Background and hypothesis. Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to selfmedicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. Proposal and conclusion. The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system. Publication Type Journal: Article Journal Name Theoretical Biology and Medical Modelling Volume 5 Year of Publication 2008 Date of Publication 2008 NEURO (A) <65> Database EMBASE Accession Number 2009196060 Authors Holmes A. Wellman C.L. Institution (Holmes) Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse, 5625 Fishers Lane, Room 2N09, Rockville, MD 20852-9411, United States. (Wellman) Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States. Country of Publication United Kingdom Title Stress-induced prefrontal reorganization and executive dysfunction in rodents. Source Neuroscience and Biobehavioral Reviews. 33(6)(pp 773-783), 2009. Date of Publication: June 2009. Publisher Elsevier Ltd Abstract The prefrontal cortex (PFC) mediates a range of higher order 'executive functions' that subserve the selection and processing of information in such a way that behavior can be planned, controlled and directed according to shifting environmental demands. Impairment of executive functions typifies many forms of psychopathology, including schizophrenia, mood and anxiety disorders and addiction, that are often associated with a history of trauma and stress. Recent research in animal models demonstrates that exposure to even brief periods of intense stress is sufficient to cause significant structural remodeling of the principle projection neurons within the rodent PFC. In parallel, there is growing evidence that stress-induced alterations in PFC neuronal morphology are associated with deficits in rodent executive functions such as working memory, attentional set-shifting and cognitive flexibility, as well as emotional dysregulation in the form of impaired fear extinction. Although the molecular basis of stress-induced changes in PFC morphology and function are only now being elucidated, an understanding of these mechanisms could provide important insight into the pathophysiology of executive dysfunction in neuropsychiatric disease and foster improved strategies for treatment. copyright 2009. ISSN 0149-7634 Publication Type Journal: Review Journal Name Neuroscience and Biobehavioral Reviews Volume 33 Issue Part 6 Page 773-783 Year of Publication 2009 Date of Publication June 2009 NEURO (A) <68> Database EMBASE Accession Number 2009199217 Authors Meyer P.J. Meshul C.K. Phillips T.J. Institution (Meshul, Phillips) Veterans Affairs Medical Center Research Service, Oregon Health and Science University, Portland, OR, United States. (Meyer, Phillips) Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States. (Meyer, Meshul, Phillips) Behavioral Neuroscience Department, Oregon Health and Science University, Portland, OR, United States. (Phillips) VA Medical Center Research Service (R and D 32), 3710 SW US Veterans Hospital Road, Portland, OR 97239, United States. Country of Publication United Kingdom Title Ethanol- and cocaine-induced locomotion are genetically related to increases in accumbal dopamine. Source Genes, Brain and Behavior. 8(3)(pp 346-355), 2009. Date of Publication: April 2009. Publisher Blackwell Publishing Ltd Abstract Neuroanatomical research suggests that interactions between dopamine and glutamate within the mesolimbic dopamine system are involved in both drug-induced locomotor stimulation and addiction. Therefore, genetically determined differences in the locomotor responses to ethanol and cocaine may be related to differences in the effects of these drugs on this system. To test this, we measured drug-induced changes in dopamine and glutamate within the nucleus accumbens (NAcc), a major target of mesolimbic dopamine neurons, using in vivo microdialysis in selectively bred FAST and SLOW mouse lines, which were bred for extreme sensitivity (FAST) and insensitivity (SLOW) to the locomotor stimulant effects of ethanol. These mice also show a genetically correlated difference in stimulant response to cocaine (FAST > SLOW). Single injections of ethanol (2 g/kg) or cocaine (40 mg/kg) resulted in larger increases in dopamine within the NAcc in FAST compared with SLOW mice. There was no effect of either drug on NAcc glutamate levels. These experiments indicate that response of the mesolimbic dopamine system is genetically correlated with sensitivity to ethanol- and cocaine-induced locomotion. Because increased sensitivity to the stimulating effects of ethanol appears to be associated with greater risk for alcohol abuse, genetically determined differences in the mesolimbic dopamine response to ethanol may represent a critical underlying mechanism for increased genetic risk for alcoholism. 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 3 Page 346-355 Year of Publication 2009 Date of Publication April 2009 NEURO (A) <95> Database EMBASE Accession Number 2009169821 Authors Bie B. Zhu W. Pan Z.Z. Institution (Bie, Zhu, Pan) Department of Anesthesiology and Pain Medicine, The University of Texas-MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 110, Houston, TX 77030, United States. Country of Publication United Kingdom Title Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala. Source Neuroscience. 160(2)(pp 348-358), 2009. Date of Publication: 05 May 2009. Publisher Elsevier Ltd Abstract Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors play an essential role in drug reward and dependence for many drugs of abuse including alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely unknown at present. Previous animal studies using systemic approaches with DOR antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease, an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR inhibition or deletion. In the present study, we used ethanol-conditioned rats to investigate adaptive DOR function in neurons of the central nucleus of the amygdala (CeA), a key brain site for alcohol reward and addiction. We found that functional DOR was absent in glutamate synapses of CeA neurons from control rats, but it emerged and inhibited glutamate synaptic currents in CeA neurons from rats displaying ethanol-induced behavior of conditioned place preference (CPP). Analysis of paired-pulse ratios and miniature glutamate synaptic currents revealed that the recruited DOR was present on glutamatergic presynaptic terminals. Similar induction of functional DOR was also found on GABA synapses. Furthermore, microinjection of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo. These results suggest that repeated alcohol exposure recruits new functional DOR on CeA glutamate and GABA synapses, which may be involved in the expression or maintenance of ethanol-induced CPP behavior. copyright 2009 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 160 Issue Part 2 Page 348-358 Year of Publication 2009 Date of Publication 05 May 2009 NEURO <96> Database EMBASE Accession Number 2009183026 Authors Chambers C.D. Garavan H. Bellgrove M.A. Institution (Chambers) School of Psychology, Cardiff University, United Kingdom. (Chambers) Institute of Cognitive Neuroscience, University College London, United Kingdom. (Garavan) Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. (Bellgrove) School of Psychology, University of Queensland, Australia. Country of Publication United Kingdom Title Insights into the neural basis of response inhibition from cognitive and clinical neuroscience. Source Neuroscience and Biobehavioral Reviews. 33(5)(pp 631-646), 2009. Date of Publication: May 2009. Publisher Elsevier Ltd Abstract Neural mechanisms of cognitive control enable us to initiate, coordinate and update behaviour. Central to successful control is the ability to suppress actions that are no longer relevant or required. In this article, we review the contribution of cognitive neuroscience, molecular genetics and clinical investigations to understanding how response inhibition is mediated in the human brain. In Section 1, we consider insights into the neural basis of inhibitory control from the effects of neural interference, neural dysfunction, and drug addiction. In Section 2, we explore the functional specificity of inhibitory mechanisms among a range of related processes, including response selection, working memory, and attention. In Section 3, we focus on the contribution of response inhibition to understanding flexible behaviour, including the effects of learning and individual differences. Finally, in Section 4, we propose a series of technical and conceptual objectives for future studies addressing the neural basis of inhibition. copyright 2008 Elsevier Ltd. All rights reserved. ISSN 0149-7634 Publication Type Journal: Review Journal Name Neuroscience and Biobehavioral Reviews Volume 33 Issue Part 5 Page 631-646 Year of Publication 2009 Date of Publication May 2009 NEURO (A) <102> Database EMBASE Accession Number 2009153469 Authors Kokarovtseva L. Jaciw-Zurakiwsky T. Mendizabal Arbocco R. Frantseva M.V. Perez Velazquez J.L. Institution (Kokarovtseva, Jaciw-Zurakiwsky, Mendizabal Arbocco, Perez Velazquez) Neuroscience and Mental Health Programme and Brain, Behaviour Centre, Division of Neurology, 555 University Avenue, Toronto, Ont. M5G1X8, Canada. (Perez Velazquez) Department of Paediatrics, Institute of Medical Science, University of Toronto, Toronto, Canada. (Frantseva) Department of Psychiatry, Centre for Addiction and Mental Health, 259 College Street, Toronto, Ont. M5T 1R8, Canada. Country of Publication United Kingdom Title Excitability and gap junction-mediated mechanisms in nucleus accumbens regulate self-stimulation reward in rats. Source Neuroscience. 159(4)(pp 1257-1263), 2009. Date of Publication: 10 Apr 2009. Publisher Elsevier Ltd Abstract The nucleus accumbens (Acb) is a part of the striatum which integrates information from cortical and limbic brain structures, and mediates behaviors which reinforce reward. Previous work has suggested that neuronal synchrony mediated by gap junctions in Acb-related areas is involved in brain pleasure and reward. In order to gain insight into functional aspects of the neural information processing at the level of the striatum, we explored the possible role of Acb gap junctional communication and chemical synapses on reward self-stimulation in rats using positive reinforcement. Rats were trained to press a lever that caused an electrical current to be delivered into the hypothalamus, which is recognized to cause pleasure/reward. Intracerebral infusion into the Acb of the gap junctional blocker carbenoxolone (CBX) decreased the lever-pressing activity. Considering that the net effect of blocking gap junctions is a reduced synchronized output of the cellular activities, which at some level represents a decrease in excitability, two other inhibitors of neuronal excitability, carbamazepine (CBZ) and tetrodotoxin (TTX), were infused into the Acb and their effects on lever-pressing assessed. All manipulations that diminished excitability in the Acb resulted in reduced lever-pressing activity. CBX and TTX were also infused into motor cortex mediating forelimb lever-pressing with no effect. However, a manipulation that has the net effect of increasing excitation, the infusion of the opiate antagonist naloxone, also decreased significantly brain self-stimulation. We conclude that reward behaviors depend to a great extent on both excitability and gap junction-mediated mechanisms in Acb neuronal networks. Thus, the Acb provides a site for the study of pleasure/reward, addiction and conscious experience. copyright 2009 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 159 Issue Part 4 Page 1257-1263 Year of Publication 2009 Date of Publication 10 Apr 2009 NEURO <113> Database EMBASE Accession Number 2009149092 Authors Philibert R.A. Gunter T.D. Beach S.R.H. Brody G.H. Hollenbeck N. Andersen A. Adams W. Institution (Philibert, Gunter, Hollenbeck, Adams) Department of Psychiatry, University of Iowa, Iowa City, IA, (Philibert) Department of Neuroscience and Genetics Programs, University of Iowa, Iowa City, IA, (Andersen) Georgetown University, Washington, DC, (Beach, Brody) University of Georgia, Athens, GA, United States. (Philibert) Department of Psychiatry, MEB Psychiatry Research/MEB, Lowa City, IA 52242-1000, United States. Country of Publication United Kingdom Title Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa Adoption Studies. Source Psychiatric Genetics. 19(2)(pp 91-98), 2009. Date of Publication: April 2009. Publisher Lippincott Williams and Wilkins Abstract Aim A number of studies have shown that genetic variatior at GABRA2 alters vulnerability to alcohol dependence. The exact identity of the causal variant(s), and the relationship of these variants to other forms of substance use and behavioral illness is, however, uncertain. Objective Therefore, we genotyped 516 individuals from the Iowa Adoption Studies, a large longitudinal case and control adoption study of substance use, at 39 single nucleotide polymorphisms encompassing the GABRA2 locus and analyzed them with respect to their lifetime history of three common forms of substance use dependence [alcohol dependence (AD), nicotine dependence (ND), and cannabis dependence (CD)] in the Iowa Adoption Studies and relevant exposure variables. Result Using regression analysis, we found substantial evidence that both GABRA2 genotype and haplotype are significantly related to vulnerability to AD, ND, and CD, witt the strongest relationships noted with respect to ND. Consistent with earlier studies suggesting exposure is an important step in the development of substance use, we found the inclusion of substance exposure data in our analytic models markedly increased the strength of the genetic associations of GABRA2 haplotype with substance use. Finally, we report that the genetic effects were markedly more pronounced in females than in males. Conclusion We conclude that genetic variation at or near the GABRA2 locus significantly affects vulnerability not only to AD, but to other forms of substance use including ND and CD, and that the effects may be sex dependent. copyright 2009 Wolters Kluwer Health. ISSN 0955-8829 Publication Type Journal: Article Journal Name Psychiatric Genetics Volume 19 Issue Part 2 Page 91-98 Year of Publication 2009 Date of Publication April 2009 NEURO <121> Database EMBASE Accession Number 2009116141 Authors Le Foll B. Gallo A. Strat Y.L. Lu L. Gorwood P. Institution (Le Foll, Gallo) Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada. (Lu) National Institute on Drug Dependence, Peking University, Beijing, China. (Strat, Gorwood) INSERM U675, University Paris VII, Paris, France. (Le Foll) Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto M5S 2S1, Canada. Country of Publication United Kingdom Title Genetics of dopamine receptors and drug addiction: A comprehensive review. Source Behavioural Pharmacology. 20(1)(pp 1-17), 2009. Date of Publication: February 2009. Publisher Lippincott Williams and Wilkins Abstract Drug dependence is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviours persist despite serious negative consequences. Addictive substances, such as opioids, ethanol, psychostimulants and nicotine, induce pleasant states or relieve distress, effects that contribute to their recreational use. Dopamine is critically involved in drug addiction processes. However, the role of the various dopaminergic receptor subtypes has been difficult to delineate. Here, we will review the information collected implicating the receptors of the D1 family (DRD1 and DRD5) and of the D2 family (DRD2, DRD 3 and DRD4) in drug addiction. We will summarize the distribution of these receptors in the brain, the preclinical experiments carried out with pharmacological and transgenic approaches and the genetic studies carried out linking genetic variants of these receptors to drug addiction phenotypes. A meta-analysis of the studies carried out evaluating DRD2 and alcohol dependence is also provided, which indicates a significant association. Overall, this review indicates that different aspects of the addiction phenotype are critically influenced by dopaminergic receptors and that variants of those genes seem to influence some addiction phenotypes in humans. copyright 2009 Wolters Kluwer Health. ISSN 0955-8810 Publication Type Journal: Review Journal Name Behavioural Pharmacology Volume 20 Issue Part 1 Page 1-17 Year of Publication 2009 Date of Publication February 2009 NEURO (GENETICS) <125> Database EMBASE Accession Number 2009134310 Authors Li M.D. Burmeister M. Institution (Li) Department of Psychiatry and Neurobehavioural Sciences, University of Virginia, 1670 Discovery Drive, Charlottesville, VA 22911, United States. (Burmeister) Molecular and Behavioral Neuroscience Institute, Departments of Psychiatry and Human Genetics, University of Michigan, 109 South Observatory Street, Ann Arbor, MI 48019, United States. Country of Publication United Kingdom Title New insights into the genetics of addiction. Source Nature Reviews Genetics. 10(4)(pp 225-231), 2009. Date of Publication: April 2009. Publisher Nature Publishing Group Abstract Drug addiction is a common brain disorder that is extremely costly to the individual and to society. Genetics contributes significantly to vulnerability to this disorder, but identification of susceptibility genes has been slow. Recent genome-wide linkage and association studies have implicated several regions and genes in addiction to various substances, including alcohol and, more recently, tobacco. Current efforts aim not only to replicate these findings in independent samples but also to determine the functional mechanisms of these genes and variants. copyright 2009 Macmillan Publishers Limited. All rights reserved. ISSN 1471-0056 Publication Type Journal: Review Journal Name Nature Reviews Genetics Volume 10 Issue Part 4 Page 225-231 Year of Publication 2009 Date of Publication April 2009