NEURO 2009 <103>Database  EMBASEAccession Number  0020175795Authors  Raffa R.B.Institution  (Raffa) Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.  Country of Publication  United KingdomTitle  The M5 muscarinic receptor as possible target for treatment of drug abuse.Source  Journal of clinical pharmacy and therapeutics.  34(6)(pp 623-629), 2009. Date of Publication: Dec 2009.Abstract  Two reports published in the latter 1980s are generally given credit for being the first to announce the discovery of a new subtype of muscarinic acetylcholine receptor (mAChR), designated m5 or M5, and now officially M(5) (1). Both identifications were assigned using molecular biology techniques. Then - as now - no selective high-affinity ligands or toxins were available. In situ hybridization and reverse-transcriptase PCR have found M(5) AChR expression in brain to be distinct from that of the four other G protein-coupled mAChR subtypes and primarily localized to the substantia nigra, ventral tegmental area, hippocampus (CA1 and CA2 subfields), cerebral cortex (outermost layer) and striatum (caudate putamen). M(5) AChR brain region localization and involvement in the regulation of striatal dopamine release and in rewarding brain stimulation suggests a possible role for M(5) AChR as a target for novel therapy to treat excess hedonic drive, including drug abuse.Publication Type  Journal: ReviewJournal Name  Journal of clinical pharmacy and therapeuticsVolume  34Issue Part  6Page  623-629Year of Publication  2009Date of Publication  Dec 2009

NEURO 2009 <162>Database  EMBASEAccession Number  2008551146Authors  Chen A.L.-C. Chen T.J.H. Waite R.L. Reinking J. Tung H.L. Rhoades P. Downs B.W. Braverman E. Braverman D. Kerner M. Blum S.H. DiNubile N. Smith D. Oscar-Berman M. Prihoda T.J. Floyd J.B. O'Brien D. Liu H.H. Blum K.Institution  (Chen, Chen) Chang Jung Christian University, Tainan, Taiwan (Republic of China).  (Chen) Changhua Christian Hospital, Changhua, Taiwan (Republic of China).  (Waite, Downs, Blum) LifeGen Inc., La Jolla, CA, United States.  (Reinking) Department of Rehabilitation Medicine, University of California, Davis Medical School, Davis, CA, United States.  (Tung) Division of Neurological Surgery, University of California School of Medicine, La Jolla, CA, United States.  (Rhoades) Comprehensive Pain Clinic, Modesto, CA, United States.  (Braverman) Department of Neurological Surgery, Weill Cornell School of Medicine, New York, NY, United States.  (Braverman, Braverman, Kerner) Department of Research, PATH Research Foundation, New York, NY, United States.  (Blum, Blum) Synaptamine Inc., San Antonio, TX, United States.  (DiNubile, Blum) Department of Orthopedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.  (Smith) Comprehensive Pain Management Clinic, San Diego, CA, United States.

  (Oscar-Berman) Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston VA Healthcare System, Boston, MA, United States.  (Prihoda) Department of Pathology, University of Texas Health Science Center, San Antonio, TX, United States.  (Floyd, O'Brien) Floyd, Skeren, and Kelly, PC, Los Angeles, CA, United States.  (Liu) Chung Shan Medical University, Taichung, Taiwan (Republic of China).  (Blum) Department Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, United States.  Country of Publication  United KingdomTitle  Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions.Source  Medical Hypotheses.  72(1)(pp 14-22), 2009. Date of Publication: January 2009.Publisher  Churchill LivingstoneAbstract  While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0306-9877Publication Type  Journal: ArticleJournal Name  Medical HypothesesVolume  72Issue Part  1Page  14-22Year of Publication  2009Date of Publication  January 2009

NEURO 2009 <587>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   20003358Status   In-Data-ReviewAuthors   Al-Zahrani MA.  Elsayed YA.Authors Full Name   Al-Zahrani, Mohamed A.  Elsayed, Yasser A.Institution  Al-Amal Complex for Mental Health, PO 5054, Dammam 31422, Saudia Arabia. yarazek68@gmail.com.Title  The impacts of substance abuse and dependence on neuropsychological functions in a sample of patients from Saudi Arabia.Source  Behavioral & Brain Functions [Electronic Resource]: BBF.  5:48, 2009.Journal Name  Behavioral & Brain Functions [Electronic Resource]: BBFOther ID  Source: NLM. PMC2799426Country of Publication  England

Abstract  ABSTRACT: BACKGROUND: A lot of studies were directed to explore the relation between drug abuse and neuropsychological functions. Some studies reported that even after a long duration of disappearance of withdrawal or intoxication symptoms, many patients have obvious deterioration of cognitive functions. The aim of this study was to explore the relationship between the substance use disorders and the executive functions. METHODS: Two groups were selected for this study. An experimental group consisted of 154 patients and further subdivided according to the substance used into three different subgroups: opioid, amphetamine and alcohol groups which included 49, 56 and 49 patients respectively. The control group was selected matching the experimental group in the demographic characteristics and included 100 healthy persons. Tools used were: Benton visual retention tests, color trail making test, Stroop colors-word test, symbol digit modalities test, the five dots cognitive flexibility test, and TAM verbal flexibility test. All the data were subjected to statistical analysis RESULTS: The study showed that the group of drug-dependent subjects performed significantly worse than the comparison group on all measures Also, there were significant differences among the subgroups as the alcoholic group was much worse followed by the amphetamine then the opioids groups. Patients with longer duration of dependence and multiple hospital readmissions were much worse in comparison to patients with shorter duration of dependence and less readmission. CONCLUSION: The study confirmed that the functions of specific brain regions underlying cognitive control are significantly impaired in patients of drug addiction. This impairment was significantly related to type of substance, duration of use and number of hospitalization and may contribute to most of behavioral disturbances found in addicts and need much attention during tailoring of treatment programs.Publication Type   Journal Article.Date of Publication   2009Year of Publication   2009Volume   5Page   48

NEURO 2009 <601>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19419578Status   In-Data-ReviewAuthors   Zhang H.  Li S.  Wang M.  Vukusic B.  Pristupa ZB.  Liu F.Authors Full Name   Zhang, Heping.  Li, Shupeng.  Wang, Min.  Vukusic, Brian.  Pristupa, Zdenek B.  Liu, Fang.Institution  Department of Neuroscience, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. fang_liu@camh.net.Title  Regulation of dopamine transporter activity by carboxypeptidase E.Source  Molecular Brain.  2(1):10, 2009.Journal Name  Molecular BrainOther ID  Source: NLM. PMC2687442Country of Publication  EnglandAbstract  ABSTRACT: BACKGROUND: The dopamine transporter (DAT) plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT) can directly interact with other cellular proteins and regulate DAT function and trafficking. RESULTS: Here, we have identified that carboxypeptidase E (CPE), a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT function. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Moreover,

coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. Functional changes caused by CPE could be attributed to enhanced DAT expression and subsequent increase in DAT cell surface localization, due to decreased DAT degradation. In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. CONCLUSION: Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity.Publication Type   Journal Article.Date of Publication   2009Year of Publication   2009Issue/Part   1Volume   2Page   10

NEURO (A) 2009 <653>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19393282Status   MEDLINEAuthors   O'Mara SM.  Sanchez-Vives MV.  Brotons-Mas JR.  O'Hare E.Authors Full Name   O'Mara, Shane M.  Sanchez-Vives, Maria V.  Brotons-Mas, Jorge R.  O'Hare, Eugene.Institution  Trinity College Institute of Neuroscience and School of Psychology, Trinity College-University of Dublin, Dublin 2, Ireland.Title  Roles for the subiculum in spatial information processing, memory, motivation and the temporal control of behaviour. [Review] [68 refs]Source  Progress in Neuro-Psychopharmacology & Biological Psychiatry.  33(5):782-90, 2009 Aug 1.Journal Name  Progress in Neuro-Psychopharmacology & Biological PsychiatryCountry of Publication  EnglandAbstract  The subiculum is in a pivotal position governing the output of the hippocampal formation. Despite this, it is a rather under-explored and sometimes ignored structure. Here, we discuss recent data indicating that the subiculum participates in a wide range of neurocognitive functions and processes. Some of the functions of subiculum are relatively well-known-these include providing a relatively coarse representation of space and participating in, and supporting certain aspects of, memory (particularly in the dynamic bridging of temporal intervals). The subiculum also participates in a wide variety of other neurocognitive functions too, however. Much less well-known are roles for the subiculum, and particularly the ventral subiculum, in the response to fear, stress and anxiety, and in the generation of motivated behaviour (particularly the behaviour that underlies drug addiction and the response to reward). There is an emerging suggestion that the subiculum participates in the temporal control of behaviour. It is notable that these latter findings have emerged from a consideration of instrumental behaviour using operant techniques; it may well be the case that the use of the watermaze or similar spatial tasks to assess subicular function (on the presumption that its functions are very similar to the hippocampus proper) has obscured rather than revealed neurocognitive functions of subiculum. The anatomy of subiculum suggests it participates in a rather subtle fashion in a very broad range of functions, rather than in a relatively more isolated fashion in a narrower range of functions, as might be the case for "earlier" components of hippocampal circuitry, such as the CA1 and CA3 subfields. Overall, there appears to a strong dorso-ventral segregation of function within subiculum, with the dorsal subiculum relatively more concerned with space and memory, and the ventral hippocampus concerned with stress, anxiety and reward. Finally, it may be the case that the whole

subiculum participates in the temporal control of reinforced behaviour, although further experimentation is required to clarify this hypothesis. [References: 68]Publication Type   Journal Article.  Research Support, Non-U.S. Gov't.  Review.Date of Publication   2009 Aug 1Year of Publication   2009Issue/Part   5Volume   33Page   782-90

NEURO (A) <666>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19616054Status   MEDLINEAuthors   Jalabert M.  Aston-Jones G.  Herzog E.  Manzoni O.  Georges F.Authors Full Name   Jalabert, Marion.  Aston-Jones, Gary.  Herzog, Etienne.  Manzoni, Olivier.  Georges, Francois.Institution  INSERM, U862, Neurocentre Magendie, Pathophysiology of synaptic plasticity group, Bordeaux, F-33000, France.Title  Role of the bed nucleus of the stria terminalis in the control of ventral tegmental area dopamine neurons.Source  Progress in Neuro-Psychopharmacology & Biological Psychiatry.  33(8):1336-46, 2009 Nov 13.Journal Name  Progress in Neuro-Psychopharmacology & Biological PsychiatryCountry of Publication  EnglandAbstract  Projections from neurons of the bed nucleus of the stria terminalis (BST) to the ventral tegmental area (VTA) are crucial to behaviors related to reward and motivation. Over the past few years, we have undertaken a series of studies to understand: 1) how excitatory inputs regulate in vivo excitable properties of BST neurons, and 2) how BST inputs in turn modulate neuronal activity of dopamine neurons in VTA. Using in vivo extracellular recording techniques in anesthetized rats and tract-tracing approaches, we have demonstrated that inputs from the infralimbic cortex and the ventral subiculum exert a strong excitatory influence on BST neurons projecting to the VTA. Thus, the BST is uniquely positioned to receive emotional and learning-associated informations and to integrate these into the reward/motivation circuitry. We will discuss how changes in the activity of BST neurons projecting to the VTA could participate in the development or exacerbation of psychiatric conditions such as drug addiction.Publication Type   Journal Article.  Research Support, Non-U.S. Gov't.Date of Publication   2009 Nov 13Year of Publication   2009Issue/Part   8Volume   33Page   1336-46

NEURO (A) <667>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19524008Status   MEDLINEAuthors   McElligott ZA.  Winder DG.Authors Full Name  McElligott, Zoe Anastasia.  Winder, Danny G.Institution  Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN, USA.

Title  Modulation of glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. [Review] [120 refs]Source  Progress in Neuro-Psychopharmacology & Biological Psychiatry.  33(8):1329-35, 2009 Nov 13.Journal Name  Progress in Neuro-Psychopharmacology & Biological PsychiatryOther ID  Source: NLM. NIHMS123689 [Available on 11/13/10]  Source: NLM. PMC2783684 [Available on 11/13/10]Country of Publication  EnglandAbstract  Glutamate, catecholamine and neuropeptide signaling within the bed nucleus of the stria terminalis (BNST) have all been identified as key participants in anxiety-like behaviors and behaviors related to withdrawal from exposure to substances of abuse. The BNST is thought to serve as a key relay between limbic cognitive centers and reward, stress and anxiety nuclei. Human studies and animal models have demonstrated that stressors and drugs of abuse can result in long term behavioral modifications that can culminate in psychological diseases such as addiction and post-traumatic stress disorder. The ability of catecholamines and neuropeptides to influence synaptic glutamatergic transmission (stemming from cognitive centers) within the BNST may have profound consequences over these behaviors. In this review we highlight studies examining synaptic plasticity and modulation of excitatory transmission within the BNST, emphasizing how such modulation may result in alterations in anxiety and reward related behavior. [References: 120]Publication Type   Journal Article.  Review.Date of Publication   2009 Nov 13Year of Publication   2009Issue/Part   8Volume   33Page   1329-35

NEURO (A) <671>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19615345Status   MEDLINEAuthors   Ji J.  Bourque M.  Di Paolo T.  Dluzen DE.Authors Full Name  Ji, Jing.  Bourque, Melanie.  Di Paolo, Therese.  Dluzen, Dean E.Institution  Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA.Title  Genetic alteration in the dopamine transporter differentially affects male and female nigrostriatal transporter systems.Source  Biochemical Pharmacology.  78(11):1401-11, 2009 Dec 1.Journal Name  Biochemical PharmacologyCountry of Publication  EnglandAbstract  Female mice with a heterozygous mutation of their dopamine transporter (+/- DAT) showed relatively robust reductions in striatal DAT specific binding (38-50%), while +/- DAT males showed modest reductions (24-32%). Significant decreases in substantia nigra DAT specific binding (42%) and mRNA (24%) were obtained in +/- DAT females, but not +/- DAT males (19% and 5%, respectively). The effects of this DAT perturbation upon vesicular monoamine

transporter-2 (VMAT-2) function revealed significantly greater reserpine-evoked DA output from +/+ and +/- DAT female as compared to male mice and the DA output profile differed markedly between +/+ and +/- DAT females, but not males. No changes in VMAT-2 protein or mRNA levels were present among these conditions. On the basis of these data, we propose: (1) a genetic mutation of the DAT does not exert equivalent effects upon the DAT in female and male mice, with females being more affected; (2) an alteration in the DAT may also affect VMAT-2 function; (3) this interaction between DAT and VMAT-2 function is more prevalent in female mice; and (4) the +/- DAT mutation affects VMAT-2 function through an indirect mechanism, that does not involve an alteration in VMAT-2 protein or mRNA. Such DAT/VMAT-2 interactions can be of significance to the gender differences observed in drug addiction and Parkinson's disease.Publication Type   Comparative Study.  Journal Article.  Research Support, Non-U.S. Gov't.Date of Publication   2009 Dec 1Year of Publication   2009Issue/Part   11Volume   78Page   1401-11

NEURO (GENETICS) <702>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19208180Status   MEDLINEAuthors   Long Q.  Zhang Q.  Ott J.Authors Full Name   Long, Quan.  Zhang, Qingrun.  Ott, Jurg.Institution  Beijing Institute of Genomics, Chinese Academy of Sciences, No, 7 Bei Tu Cheng West Road, Beijing 100029, PR China. ql2@sanger.ac.ukTitle  Detecting disease-associated genotype patterns.Source  BMC Bioinformatics.  10 Suppl 1:S75, 2009.Journal Name  BMC BioinformaticsOther ID  Source: NLM. PMC2648768Country of Publication  EnglandAbstract  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.Publication Type   Journal Article.  Research Support, N.I.H., Extramural.  Research Support, Non-U.S. Gov't.Date of Publication   2009Year of Publication  2009

Volume   10 Suppl 1Page   S75

NEURO 2009 <704>Database   Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)Unique Identifier   19174218Status   MEDLINEAuthors   Mercolini L.  Gerra G.  Consorti M.  Somaini L.  Raggi MA.Authors Full Name   Mercolini, Laura.  Gerra, Gilberto.  Consorti, Marco.  Somaini, Lorenzo.  Raggi, Maria Augusta.Institution  Faculty of Pharmacy, Department of Pharmaceutical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.Title  Fast analysis of catecholamine metabolites MHPG and VMA in human plasma by HPLC with fluorescence detection and a novel SPE procedure.Source  Talanta.  78(1):150-5, 2009 Apr 15.Journal Name  TalantaCountry of Publication  EnglandAbstract  A fast and sensitive high-performance liquid chromatographic method has been developed for the determination in human plasma of MHPG (3-methoxy-4-hydroxyphenylethylenglycol) and VMA (vanillyl mandelic acid), the main metabolites of epinephrine and norepinephrine. Analyses were carried out at 325 nm while exciting at 285 nm on a reversed-phase column (Atlantis C18, 150 mm x 4.6 mm I.D., 5 microm) using a mobile phase composed of 2% methanol and 98% aqueous citrate buffer at pH 3.0. A careful solid-phase extraction procedure, based on mixed-mode reversed-phase - strong anion exchange Oasis cartridges (MAX, 30 mg, 1 mL), was developed for the pre-treatment of plasma samples. Extraction yields were satisfactory, always higher than 90%. Calibration curves were linear over the 0.2-40.0 ng mL(-1) concentration range for MHPG and over the 0.5-40.0 ng mL(-1) concentration range for VMA. The method was successfully applied to plasma samples of former drug users undergoing detoxification therapy and subjects "at risk" of developing drug addiction.Publication Type   Journal Article.  Research Support, Non-U.S. Gov't.Date of Publication   2009 Apr 15Year of Publication   2009Issue/Part   1Volume   78Page   150-5

NEURO 2009 <142>Database  EMBASEAccession Number  2009108380Authors  Weitemier A.Z. Murphy N.P.Institution  (Weitemier, Murphy) Molecular Neuropathology Research Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wakoshi, Saitama 351-0198, Japan.  Country of Publication  United KingdomTitle  Accumbal dopamine and serotonin activity throughout acquisition and expression of place conditioning: Correlative relationships with preference and aversion.Source  European Journal of Neuroscience.  29(5)(pp 1015-1026), 2009. Date of Publication: March 2009.

Publisher  Blackwell Publishing LtdAbstract  The ability of addictive drugs to induce adaptations in mesolimbic dopamine (DA) activity offers an attractive neurobiological explanation for enhanced incentive motivation toward drug-associated stimuli in addiction. However, direct evidence supporting this is sparse. By tracking neurochemical activity within the mouse nucleus accumbens via microdialysis during repeated pairing of morphine with environmental stimuli, we reveal a predictive relationship between enhanced DA responses to morphine and subsequent preference towards a morphine-paired stimulus. A similar relationship for serotonin (5-HT) was observed, suggesting that these neuromodulatory systems work in concert. During expression of preference towards a morphine-paired stimulus, extracellular DA was not enhanced but was negatively associated with this behavior on a subject-by-subject basis. In contrast, avoidance of an aversively-paired stimulus (the opiate antagonist naloxone) was associated with enhanced extracellular DA levels, and also the balance between DA and 5-HT responses. These findings reveal a tangible predictive relationship between drug-induced neural adaptations and conditioned behavior, and emphasize that DA activity is not generalized to all subcomponents of behavior conditioned by addictive drugs. They further provide evidence for an active role of DA-5-HT interactions in the expression of learned behavior. copyright Federation of European Neuroscience Societies and Blackwell Publishing Ltd.ISSN  0953-816XPublication Type  Journal: ArticleJournal Name  European Journal of NeuroscienceVolume  29Issue Part  5Page  1015-1026Year of Publication  2009Date of Publication  March 2009

NEURO 2009 <145>Database  EMBASEAccession Number  2009101570Authors  Traynor J.R. Terzi D. Caldarone B.J. Zachariou V.Institution  (Traynor) Department of Pharmacology, Substance Abuse Research Center, University of Michigan, Ann Arbor, MI 48109, United States.  (Terzi, Zachariou) Department of Pharmacology, University of Crete Faculty of Medicine, Heraklion, 71003 Crete, Greece.  (Caldarone) PsychoGenics, 765 Old Saw Mill River, Road, Tarrytown, NY 10591, United States.  Country of Publication  United KingdomTitle  RGS9-2: probing an intracellular modulator of behavior as a drug target.Source  Trends in Pharmacological Sciences.  30(3)(pp 105-111), 2009. Date of Publication: March 2009.Publisher  Elsevier LtdAbstract  Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction. This protein negatively modulates signal transduction thus playing a key part in striatal function and resultant behavioral responses. In particular, there is evidence of important interactions with mu-opioid- and dopamine D2-receptor signaling pathways. Several studies indicate that manipulations of RGS9-2 levels in the striatum might greatly affect pharmacological responses. These findings

indicate that treatment strategies targeting RGS9-2 levels or activity might be used to enhance responses to drugs acting at GPCRs and/or prevent undesired drug actions. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0165-6147Publication Type  Journal: ArticleJournal Name  Trends in Pharmacological SciencesVolume  30Issue Part  3Page  105-111Year of Publication  2009Date of Publication  March 2009

NEURO 2009 <146>Database  EMBASEAccession Number  2009098514Authors  Brami-Cherrier K. Roze E. Girault J.-A. Betuing S. Caboche J.Institution  (Brami-Cherrier, Roze, Betuing, Caboche) UMRS 952, INSERM, Universite Pierre et Marie Curie-Paris-6, Paris, France.  (Brami-Cherrier, Girault) UMR-S 839, Inserm, Institut du Fer A Moulin, Paris, France.  (Roze) Pole des Maladies du Systeme Nerveux, Federation de Neurologie, AP-HP, Paris, France.(Betuing) Universite d'Evry Val d'Essonne, Boulevard Francois Mitterand, Evry, Cedex, France.  (Caboche) UMRS 952, INSERM, Universite Pierre et Marie Curie-Paris-6, 9 quai Saint Bernard, 75005 Paris, France.  Country of Publication  United KingdomTitle  Role of the ERK/MSK1 signalling pathway in chromatin remodelling and brain responses to drugs of abuse.Source  Journal of Neurochemistry.  108(6)(pp 1323-1335), 2009. Date of Publication: March 2009.Publisher  Blackwell Publishing LtdAbstract  Drugs of abuse induce neuroadaptations through regulation of gene expression. Although much attention has focused on transcription factor activities, new concepts have recently emerged on the role of chromatin remodelling as a prerequisite for regulation of gene expression in neurons. Thus, for transcription to occur, chromatin must be decondensed, a dynamic process that depends on post-translational modifications of histones. We review here these modifications with a particular emphasis on the role of histone H3 phosphorylation at the promoter of specific genes, including c-fos and c-jun. We trace the signalling pathways involved in H3 phosphorylation and provide evidence for a role of mitogen and stress-activated protein kinase-1 (MSK1) downstream from the MAPK/extracellular-signal regulated kinase (ERK) cascade. In response to cocaine, MSK1 controls an early phase of histone H3 phosphorylation at the c-fos promoter in striatal neurons. MSK1 action may be potentiated by the concomitant inhibition of protein phosphatase 1 by nuclear translocation of dopamine- and cAMP-regulated phosphoprotein Mr = 32 000. H3 phosphorylation by MSK1 is critically involved in c-fos transcription, and cocaine-induced locomotor sensitization. Thus, ERK plays a dual role in gene regulation and drug addiction by direct activation of transcription factors and by chromatin remodelling. copyright 2009 International Society for Neurochemistry.ISSN  0022-3042Publication Type  Journal: ReviewJournal Name  Journal of NeurochemistryVolume  108Issue Part  6Page  1323-1335Year of Publication  2009

Date of Publication  March 2009

NEURO 2009 <161>Database  EMBASEAccession Number  2009086563Authors  Buydens-Branchey L. Branchey M. Hibbeln J.R.Institution  (Buydens-Branchey) Psychiatry Service, DVA New York Harbor Healthcare System, Brooklyn, NY, United States.  (Branchey, Hibbeln) National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States.  (Buydens-Branchey) Narrows Institute for Biomedical Research, 800 Poly Place, Brooklyn, NY 11209, United States.  Country of Publication  United KingdomTitle  Low plasma levels of docosahexaenoic acid are associated with an increased relapse vulnerability in substance abusers.Source  American Journal on Addictions.  18(1)(pp 73-80), 2009. Date of Publication: January 2009.Publisher  Informa HealthcareAbstract  Low levels of some polyunsaturated fatty acids (PUFAs) could influence behaviors leading to the abuse of substances through their actions on serotonergic and dopaminergic mechanisms. Because substance abusers tend to have poor dietary habits, the possibility that a deficient intake of n-3 PUFAs, available from dietary sources only, and subsequent low n-3 plasma levels would predict their relapse rates was explored. Thirty-five patients admitted to substance abuse clinics were enrolled and followed for one year. Dietary questionnaires and blood samples were collected at baseline and on a quarterly basis, and relapse rates monitored on a monthly basis. Six patients dropped out shortly after study entry, 11 relapsed in the course of the study and dropped out, 7 relapsed but completed the study, and 11 did not relapse and completed the study. Non-relapsers were found to have significantly higher levels of docosahexaenoic acid (DHA) calculated as mug/ml and % TFA, when compared to relapsers (p =.031 and p =.010, respectively) and to relapsers and non-completers combined (p =.014 and p =.009, respectively). These pilot data suggest, but do not prove, the existence of a relationship between low levels of DHA and relapse vulnerability in some individuals who abuse substances. The study of the efficacy of n-3 supplements or of dietary modifications on relapse appears warranted. Copyright copyright American Academy of Addiction Psychiatry.ISSN  1055-0496Publication Type  Journal: ArticleJournal Name  American Journal on AddictionsVolume  18Issue Part  1Page  73-80Year of Publication  2009Date of Publication  January 2009

NEURO 2009 <178>Database  EMBASEAccession Number  2009057502Authors  Carter M.E. Borg J.S. de Lecea L.Institution  (Carter, Borg, de Lecea) Department of Psychiatry and Behavioral Sciences, Stanford University, 701B Welch Road, Palo Alto, CA 94304, United States.  Country of Publication  United KingdomTitle

  The brain hypocretins and their receptors: mediators of allostatic arousal.Source  Current Opinion in Pharmacology.  9(1)(pp 39-45), 2009. Date of Publication: February 2009.Publisher  Elsevier LtdAbstract  The hypocretins (abbreviated 'Hcrts' - also called 'orexins') are two neuropeptides secreted exclusively by a small population of neurons in the lateral hypothalamus. These peptides bind to two receptors located throughout the brain in nuclei associated with diverse cognitive and physiological functions. Initially, the brain Hcrt system was found to have a major role in the regulation of sleep/wake transitions. More recent studies indicate Hcrts may play a role in other physiological functions, including food intake, addiction, and stress. Taken together, these studies suggest a general role for Hcrts in mediating arousal, especially when an organism must respond to unexpected stressors and challenges in the environment. copyright 2009.ISSN  1471-4892Publication Type  Journal: ReviewJournal Name  Current Opinion in PharmacologyVolume  9Issue Part  1Page  39-45Year of Publication  2009Date of Publication  February 2009

NEURO 2009 <181>Database  EMBASEAccession Number  2009057501Authors  Kreek M.J. Zhou Y. Butelman E.R. Levran O.Institution  (Kreek, Zhou, Butelman, Levran) The Rockefeller University, Laboratory of the Biology of Addictive Diseases, 1230 York Avenue, New York, NY 10065, United States.  Country of Publication  United KingdomTitle  Opiate and cocaine addiction: from bench to clinic and back to the bench.Source  Current Opinion in Pharmacology.  9(1)(pp 74-80), 2009. Date of Publication: February 2009.Publisher  Elsevier LtdAbstract  This review primarily focuses on our recent findings in bidirectional translational research on opiate and cocaine addictions. First, we present neurobiological and molecular studies on endogenous opioid systems (e.g. proopiomelanocortin, mu opioid receptor, dynorphin, and kappa opioid receptor), brain stress-responsive systems (e.g. orexin, arginine vasopressin, V1b receptor, and corticotropin-releasing factor), hypothalamic-pituitary-adrenal axis, and neurotransmitters (especially dopamine), in response to both chronic cocaine or opiate exposure and to drug withdrawal, using several newly developed animal models and molecular approaches. The second aspect is human molecular genetic association investigations including hypothesis-driven studies and genome-wide array studies, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy. copyright 2009.ISSN  1471-4892Publication Type  Journal: ReviewJournal Name  Current Opinion in PharmacologyVolume  9

Issue Part  1Page  74-80Year of Publication  2009Date of Publication  February 2009

NEURO 2009 <182>Database  EMBASEAccession Number  2009057493Authors  De Mei C. Ramos M. Iitaka C. Borrelli E.Institution  (De Mei, Ramos, Iitaka, Borrelli) University of California Irvine, Department of Microbiology and Molecular Genetics, 3113 Gillespie NRF, Irvine, CA 92617, United States.  Country of Publication  United KingdomTitle  Getting specialized: presynaptic and postsynaptic dopamine D2 receptors.Source  Current Opinion in Pharmacology.  9(1)(pp 53-58), 2009. Date of Publication: February 2009.Publisher  Elsevier LtdAbstract  Dopamine (DA) signaling controls many physiological functions ranging from locomotion to hormone secretion, and plays a critical role in addiction. DA elevation, for instance in response to drugs of abuse, simultaneously activates neurons expressing different DA receptors; how responses from diverse neurons/receptors are orchestrated in the generation of behavioral and cellular outcomes, is still not completely defined. Signaling from D2 receptors (D2Rs) is a good example to illustrate this complexity. D2Rs have presynaptic and postsynaptic localization and functions, which are shared by two isoforms in vivo. Recent results from knockout mice are clarifying the role of site and D2 isoform-specific effects thereby increasing our understanding of how DA modulates neuronal physiology. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  1471-4892Publication Type  Journal: ReviewJournal Name  Current Opinion in PharmacologyVolume  9Issue Part  1Page  53-58Year of Publication  2009Date of Publication  February 2009

NEURO 2009 <184>Database  EMBASEAccession Number  2009000502Authors  Stella N.Institution  (Stella) Department of Pharmacology, Psychiatry and Behavioral Sciences, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-7280, United States.  Country of Publication  United KingdomTitle  Endocannabinoid signaling in microglial cells.Source  Neuropharmacology.  56(SUPPL. 1)(pp 244-253), 2009. Date of Publication: 2009.Publisher  Elsevier Ltd

Abstract  The endocannabinoid signaling system (eCBSS) is composed of cannabinoid (CB) receptors, their endogenous ligands (the endocannabinoids, eCB) and the enzymes that produce and inactivate these ligands. Neurons use this signaling system to communicate with each other and Delta9-tetrahydrocannabinol (THC), the main psychotropic ingredient of Cannabis sativa, induces profound behavioral effects by impinging on this communication. Evidence now shows that microglia, the macrophages of the brain, also express a functional eCBSS and that activation of CB receptors expressed by activated microglia controls their immune-related functions. This review summarizes this evidence, discusses how microglia might use the eCBSS to communicate with each other and neighboring cells, and argues that compounds selectively targeting the eCBSS expressed by microglia constitute valuable therapeutics to manage acute and chronic neuroinflammation, without inducing the psychotropic effects and underlying addictive properties commonly associated with THC.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  244-253Yearof Publication  2009Date of Publication  2009

NEURO 2009 <187>Database  EMBASEAccession Number  2009000504Authors  Koob G.F.Institution  (Koob) Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, United States.  Country of Publication  United KingdomTitle  Neurobiological substrates for the dark side of compulsivity in addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 18-31), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Drug addiction can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, increases in anxiety-like responses, and increases in extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of addiction. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to

the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least in part, the compulsivity of addiction. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  18-31Year of Publication  2009Date of Publication  2009

NEURO 2009 <188>Database  EMBASEAccession Number  2009000491Authors  Haydon P.G. Blendy J. Moss S.J. Rob Jackson F.Institution  (Haydon, Moss) Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States.  (Blendy) Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States.  (Haydon, Moss, Rob Jackson) Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, United States.  Country of Publication  United KingdomTitle  Astrocytic control of synaptic transmission and plasticity: a target for drugs of abuse?Source  Neuropharmacology.  56(SUPPL. 1)(pp 83-90), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  It is well recognized that drugs of abuse lead to plastic changes in synapses and that these long-term modifications have the potential to underlie adaptive changes of the brain that lead to substance abuse. However the variety of molecular mechanisms involved in these responses are not completely defined. We are just beginning to understand some of the roles of glial cells that are associated with synapses. At many synapses an astrocyte process is associated with pre- and postsynaptic neuron processes leading to the naming of this synaptic structure as the Tripartite Synapse. Therefore, these glial cells are positioned so that they influence synaptic transmission and thus could potentially regulate the actions of some drugs of abuse. In mammalian systems there are correlations between long-term structural changes in astrocytes and responses to drugs of abuse. However, whether such changes in glia impact brain function and subsequent behaviors associated with addiction is poorly understood. Studies using Drosophila show important roles of fly glia in mediating responses to cocaine pointing to the potential for the involvement of mammalian glia in the brain's responses to this as well as other drugs. In agreement with this possibility three receptor systems known to be important in substance abuse, mGluR5, GABAB and CB-1 receptors, are all expressed by astrocytes and the activation of these glial receptors is now known to impact neuronal excitability and synaptic transmission. Given our new knowledge about the presence of reciprocal signaling between astrocytes and synapses we are now at a time when it becomes appropriate to determine how glial cells respond to drugs of abuse and whether they contribute to the changes in brain function underlying substance abuse. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908

Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  83-90Year of Publication  2009Date of Publication  2009

NEURO 2009 <190>Database  EMBASEAccession Number  2009000501Authors  Verdejo-Garcia A. Bechara A.Institution  (Verdejo-Garcia) Department of Clinical Psychology, Institute of Neuroscience, Universidad de Granada, Spain.  (Bechara) Brain and Creativity Institute, University of Southern California, HEDCO Neuroscience Building, 3641 Watt Way, Suite B26, Los Angeles, CA 90089-2520, United States.  Country of Publication  United KingdomTitle  A somatic marker theory of addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 48-62), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. Growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioral studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of "craving", including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent to which these studies support a somatic marker theory of addiction. We conclude that there are at least two underlying types of dysfunction where emotional signals (somatic markers) turn in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  48-62Year of Publication  2009Date of Publication  2009

NEURO 2009 <191>

Database  EMBASEAccession Number  2009006611Authors  Romanova E.V. Hatcher N.G. Rubakhin S.S. Sweedler J.V.Institution  (Romanova, Hatcher, Rubakhin, Sweedler) Department of Chemistry, Beckman Institute, University of Illinois, 600 South Mathews Avenue 63-5, Urbana, IL 61801, United States.  Country of Publication  United KingdomTitle  Characterizing intercellular signaling peptides in drug addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 196-204), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Intercellular signaling peptides (SPs) coordinate the activity of cells and influence organism behavior. SPs, a chemically and structurally diverse group of compounds responsible for transferring information between neurons, are broadly involved in neural plasticity, learning and memory, as well as in drug addiction phenomena. Historically, SP discovery and characterization has tracked advances in measurement capabilities. Today, a suite of analytical technologies is available to investigate individual SPs, as well as entire intercellular signaling complements, in samples ranging from individual cells to entire organisms. Immunochemistry and in situ hybridization are commonly used for following preselected SPs. Discovery-type investigations targeting the transcriptome and proteome are accomplished using high-throughput characterization technologies such as microarrays and mass spectrometry. By integrating directed approaches with discovery approaches, multiplatform studies fill critical gaps in our knowledge of drug-induced alterations in intercellular signaling. Throughout the past 35 years, the National Institute on Drug Abuse has made significant resources available to scientists that study the mechanisms of drug addiction. The roles of SPs in the addiction process are highlighted, as are the analytical approaches used to detect and characterize them. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  196-204Year of Publication  2009Date of Publication  2009

NEURO 2009 <192>Database  EMBASEAccession Number 2009000498Authors  Bonci A. Borgland S.Institution  (Bonci) Ernest Gallo Clinic, Research Center, University of California, San Francisco, United States.  (Bonci) Department of Neurology, University of California, San Francisco, United States.  (Borgland) Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Rm 212, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.  Country of Publication  United KingdomTitle  Role of orexin/hypocretin and CRF in the formation of drug-dependent synaptic plasticity in the mesolimbic system.Source  Neuropharmacology.  56(SUPPL. 1)(pp 107-111), 2009. Date of Publication: 2009.Publisher

  Elsevier LtdAbstract  Dopamine neurons in the ventral tegmental area (VTA) play a very important role in a variety of physiological as well as addictive behaviors. However, a clear understanding of the cellular mechanisms underlying these behaviors is still missing. Within the VTA, recent studies have shown that forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are produced by drugs of abuse. The main goal of this review is to discuss the relationship between plasticity at excitatory synapses in the VTA and addiction-associated behaviors such as behavioral sensitization and cocaine self-administration. Furthermore, recent studies have highlighted the role of orexin/hypocretin and corticotropin-releasing factor (CRF) as powerful modulators of excitatory synaptic transmission in the VTA. Here, we will discuss the potential correlation between the ability of these peptides in mediating excitatory synaptic transmission and the development of stress- and drug-dependent behaviors. Taken together, the results from the studies reviewed here shed new light on the mechanistic role of plasticity at glutamatergic synapses in the VTA in mediating addictive, as well as stress-dependent behaviors.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  107-111Year of Publication  2009Date of Publication  2009

NEURO 2009 <196>Database  EMBASEAccession Number  2009000485Authors  Aston-Jones G. Smith R.J. Moorman D.E. Richardson K.A.Institution  (Aston-Jones, Smith, Moorman, Richardson) Department of Neurosciences, Medical University of South Carolina, Basic Science Bldg. 403, 173 Ashley Ave., Charleston, SC 29425-5100, United States.  Country of Publication  United KingdomTitle  Role of lateral hypothalamic orexin neurons in reward processing and addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 112-121), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Orexins (also known as hypocretins) are recently discovered neuropeptides made exclusively in hypothalamic neurons that have been shown to be important in narcolepsy/cataplexy and arousal. Here, we conducted behavioral, anatomical and neurophysiological studies that show that a subset of these cells, located specifically in lateral hypothalamus (LH), are involved in reward processing and addictive behaviors. We found that Fos expression in LH orexin neurons varied in proportion to preference for morphine, cocaine or food. This relationship obtained both in drug naive rats and in animals during protracted morphine withdrawal, when drug preference was elevated but food preference was decreased. Recent studies showed that LH orexin neurons that project to ventral tegmental area (VTA) have greater Fos induction in association with elevated morphine preference during protracted withdrawal than non-VTA-projecting orexin neurons, indicating that the VTA is an important site of action for orexin's role in reward processing. In addition, we found that stimulation of LH orexin neurons, or microinjection of orexin into VTA, reinstated an extinguished morphine preference. Most recently, using a self-administration paradigm we discovered that the Ox1 receptor antagonist SB-334867 (SB) blocks cocaine-seeking induced

by discrete or contextual cues, but not by a priming injection of cocaine. Neurophysiological studies revealed that locally applied orexin often augmented responses of VTA dopamine (DA) neurons to activation of the medial prefrontal cortex (mPFC), consistent with the view that orexin facilitates activation of VTA DA neurons by stimulus-reward associations. We also recently showed that orexin in VTA is necessary for learning a morphine place preference. These findings are consistent with results from others showing that orexin facilitates glutamate-mediated responses, and is necessary for glutamate-dependent long-term potentiation, in VTA DA neurons. We surmise from these studies that LH orexin neurons play an important role in reward processing and addiction, and that LH orexin cells are an important input to VTA for behavioral effects associated with reward-paired stimuli. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  112-121Year of Publication  2009Date of Publication  2009

NEURO 2009 <198>Database  EMBASEAccession Number  2009002882Authors  Kalivas P.W. LaLumiere R.T. Knackstedt L. Shen H.Institution  (Kalivas, LaLumiere, Knackstedt, Shen) Department of Neurosciences, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29464, United States.  Country of Publication  United KingdomTitle  Glutamate transmission in addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 169-173), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Cortico-striatal glutamate transmission has been implicated in both the initiation and expression of addiction related behaviors, such as locomotor sensitization and drug-seeking. While glutamate transmission onto dopamine cells in the ventral tegmental area undergoes transient plasticity important for establishing addiction-related behaviors, glutamatergic plasticity in the nucleus accumbens is critical for the expression of these behaviors. This information points to the value of exploring pharmacotherapeutic manipulation of glutamate plasticity in treating drug addiction. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  169-173Year of Publication  2009Date of Publication  2009

NEURO 2009 <199>Database  EMBASEAccession Number  2009000492Authors  Carlezon Jr. W.A. Thomas M.J.

Institution  (Carlezon Jr.) Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, MRC 217, 115 Mill Street, Belmont, MA 02478, United States.  (Thomas) Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States.  (Thomas) Department of Psychology, University of Minnesota, Minneapolis, MN 55455, United States.  Country of Publication  United KingdomTitle  Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis.Source  Neuropharmacology.  56(SUPPL. 1)(pp 122-132), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  The nucleus accumbens (NAc) is a critical element of the mesocorticolimbic system, a brain circuit implicated in reward and motivation. This basal forebrain structure receives dopamine (DA) input from the ventral tegmental area (VTA) and glutamate (GLU) input from regions including the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP). As such, it integrates inputs from limbic and cortical regions, linking motivation with action. The NAc has a well-established role in mediating the rewarding effects of drugs of abuse and natural rewards such as food and sexual behavior. However, accumulating pharmacological, molecular, and electrophysiological evidence has raised the possibility that it also plays an important (and sometimes underappreciated) role in mediating aversive states. Here we review evidence that rewarding and aversive states are encoded in the activity of NAc medium spiny GABAergic neurons, which account for the vast majority of the neurons in this region. While admittedly simple, this working hypothesis is testable using combinations of available and emerging technologies, including electrophysiology, genetic engineering, and functional brain imaging. A deeper understanding of the basic neurobiology of mood states will facilitate the development of well-tolerated medications that treat and prevent addiction and other conditions (e.g., mood disorders) associated with dysregulation of brain motivation systems. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  122-132Year of Publication  2009Date of Publication  2009

NEURO (A) 2009 <200>Database  EMBASEAccession Number  2009000493Authors  Vezina P. Leyton M.Institution  (Vezina) Department of Psychiatry, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, United States.  (Leyton) Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Que. H3A 1A1, Canada.  Country of Publication  United KingdomTitle  Conditioned cues and the expression of stimulant sensitization in animals and humans.Source  Neuropharmacology.  56(SUPPL. 1)(pp 160-168), 2009. Date of Publication: 2009.Publisher

  Elsevier LtdAbstract  Repeated intermittent exposure to psychostimulants can lead to long-lasting sensitization of the drugs' behavioral and biochemical effects. Such findings have figured importantly in recent theories of drug addiction proposing that sensitized nucleus accumbens (NAcc) dopamine (DA) overflow in particular acts in concert with other alterations in the neurochemistry of this nucleus to promote drug seeking and self-administration. Yet, experiments in rodents, non-human primates and humans have not always detected behavioral or biochemical sensitization following drug exposure, bringing into doubt the utility of this model. In an effort to reconcile apparent discrepancies in the literature, this review assesses conditions that might affect the expression of sensitization during testing. Specifically, the role played by conditioned cues is reviewed. A number of reports strongly support a potent and critical role for conditioned stimuli in the expression of sensitization. Findings suggest that stimuli associated either with the presence or absence of drug can respectively facilitate or inhibit sensitized responding. It is concluded that the presence or absence of such stimuli during testing for sensitization in animal and human studies could significantly affect the results obtained. It is necessary to consider this possibility especially when interpreting the results of studies that fail to observe sensitized responding. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  160-168Year of Publication  2009Date of Publication  2009

NEURO 2009 <201>Database  EMBASEAccession Number  2009000490Authors  Falcon E. McClung C.A.Institution  (Falcon, McClung) Department of Psychiatry, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, United States.  Country of Publication  United KingdomTitle  A role for the circadian genes in drug addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 91-96), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Diurnal and circadian rhythms are prominent in nearly all bodily functions. Chronic disruptions in normal sleep wake and social schedules can lead to serious health problems such as those seen in shift worker's syndrome. Moreover, genetic disruptions in normal circadian gene functions have recently been linked to a variety of psychiatric conditions including depression, bipolar disorder, seasonal affective disorder and alcoholism. Recent studies are beginning to determine how these circadian genes and rhythms are involved in the development of drug addiction. Several of these studies suggest an important role for these genes in limbic regions of the brain, outside of the central circadian pacemaker in the suprachiasmatic nucleus (SCN). This review summarizes some of the basic research into the importance of circadian genes in drug addiction. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: Review

Journal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  91-96Year of Publication  2009Date of Publication  2009

NEURO 2009 <202>Database  EMBASEAccession Number  2009000486Authors  Russo S.J. Mazei-Robison M.S. Ables J.L. Nestler E.J.Institution  (Russo, Mazei-Robison, Ables, Nestler) Fishberg Department of Neuroscience, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, United States.  Country of Publication  United KingdomTitle  Neurotrophic factors and structural plasticity in addiction.Source  Neuropharmacology.  56(SUPPL. 1)(pp 73-82), 2009. Date of Publication: 2009.Publisher  Elsevier LtdAbstract  Drugs of abuse produce widespread effects on the structure and function of neurons throughout the brain's reward circuitry, and these changes are believed to underlie the long-lasting behavioral phenotypes that characterize addiction. Although the intracellular mechanisms regulating the structural plasticity of neurons are not fully understood, accumulating evidence suggests an essential role for neurotrophic factor signaling in the neuronal remodeling which occurs after chronic drug administration. Brain-derived neurotrophic factor (BDNF), a growth factor enriched in brain and highly regulated by several drugs of abuse, regulates the phosphatidylinositol 3'-kinase (PI3K), mitogen-activated protein kinase (MAPK), phospholipase Cgamma (PLCgamma), and nuclear factor kappa B (NFkappaB) signaling pathways, which influence a range of cellular functions including neuronal survival, growth, differentiation, and structure. This review discusses recent advances in our understanding of how BDNF and its signaling pathways regulate structural and behavioral plasticity in the context of drug addiction. copyright 2008 Elsevier Ltd. All rights reserved.ISSN  0028-3908Publication Type  Journal: ReviewJournal Name  NeuropharmacologyVolume  56Issue Part  SUPPL. 1Page  73-82Year of Publication  2009Date of Publication  2009