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NEURO 2007 <889> Database EMBASE Accession Number 2007542706 Authors Wall T.L. Schoedel K. Ring H.Z. Luczak S.E. Katsuyoshi D.M. Tyndale R.F. Institution (Wall) Department of Psychiatry, University of California, San Diego, Veterans Medical Research Foundation, San Diego, CA, United States. (Schoedel) Decision Line Clinical Research Corporation, Toronto, ON, Canada. (Ring) DNA Direct Inc., San Francisco, CA, United States. (Luczak) Department of Psychology, University of Southern California, Los Angeles, CA, United States. (Katsuyoshi) Center for Health Sciences, SRI International, Menlo Park, CA, United States. (Tyndale) Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, ON, Canada. Country of Publication United Kingdom Title Differences in pharmacogenetics of nicotine and alcohol metabolism: Review and recommendations for future research. Source Nicotine and Tobacco Research. 9(SUPPL. 3)(pp S459-S474), 2007. Date of Publication: Nov 2007. Abstract Genetic variations in the enzymes involved in alcohol and nicotine metabolism can profoundly affect the rates of metabolism of these drugs, which in turn can influence drugtaking behaviors. The frequency of these genetic variants differs substantially among ethnic groups, resulting in differing genetic influences, or degrees of risk, among different populations. For many of these enzymatic pathways, the genetic variations that affect the rates of metabolism are very different in Asians and Caucasians and may contribute to population differences in alcohol- and tobacco-related behaviors and diseases. Understanding how variations in alcohol- and nicotine-metabolizing enzymes alter these drug responses and behaviors, with special focus on genetic variations, is the subject of this review. Each section describes genetic variations in a particular enzymatic pathway and reviews what is known about population variation and the resulting impact on alcohol- and/or nicotine-related disorders. Each section concludes with some thoughts on future research priorities. Sections 1 and 2 review the primary alcohol- and acetaldehyde-metabolizing enzymes and provide a working model for how the genetic variations in these enzymes may affect alcohol consumption and related disorders. Section 1 focuses on the alcohol and acetaldehyde dehydrogenases, while section 2 focuses on CYP2E1 and its possible role in alcohol and tobacco dependence. Sections 3 and 4 describe enzymes involved in nicotine metabolism, with section 3 focusing on the major nicotine-to-cotinine metabolizing enzyme, CYP2A6, and how genetically differing rates of metabolic inactivation of nicotine alter smoking. Section 4 describes data on the many additional enzymes involved in the metabolism of nicotine and its metabolites and summarizes our current understanding of the influence these enzymes may have on metabolism and addiction in this relatively new research area. ISSN 1462-2203 Publication Type Journal: Review Journal Name Nicotine and Tobacco Research Volume 9 Issue Part SUPPL. 3 Page S459-S474 Year of Publication 2007 Date of Publication Nov 2007 NEURO (GENETICS) 2007 <891> Database EMBASE Accession Number 2007527795 Authors Yano M. Steiner H. Institution (Yano, Steiner) Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, United States. Country of Publication United Kingdom Title Methylphenidate and cocaine: the same effects on gene regulation? Source Trends in Pharmacological Sciences. 28(11)(pp 588-596), 2007. Date of Publication: Nov 2007. Abstract Methylphenidate (Ritalin), a psychostimulant used in the treatment of Attention-Deficit Hyperactivity Disorder, has pharmacological effects similar to cocaine and amphetamine. Clinical use of methylphenidate, as well as diversion and abuse, have significantly increased during the past 10-15 years, heightening concerns regarding the long-term effects of methylphenidate on the developing brain. Here we review the effects of acute and repeated methylphenidate treatment on molecules of neuronal signaling and neuroplasticity (including transcription factors, neuropeptides, and components of second messenger cascades) and compare these molecular effects with those produced by cocaine and amphetamine. Some molecular changes, such as altered transcription factor gene regulation, are similar to those of cocaine and amphetamine. Other effects, notably those on the expression of opioid peptides and postsynaptic density molecules (Homer 1a), differ between methylphenidate and cocaine or amphetamine treatment. These differences support the notion that methylphenidate produces less neuroadaptations than cocaine and amphetamine, and might provide a molecular basis for reduced addiction liability of methylphenidate compared with these other psychostimulants. copyright 2007 Elsevier Ltd. All rights reserved. ISSN 0165-6147 Publication Type Journal: Review Journal Name Trends in Pharmacological Sciences Volume 28 Issue Part 11 Page 588-596 Year of Publication 2007 Date of Publication Nov 2007 NEURO 2007 <892> Database EMBASE Accession Number 2007527792 Authors Rashid A.J. O'Dowd B.F. Verma V. George S.R. Institution (Rashid, O'Dowd, Verma, George) Department of Pharmacology, University of Toronto, Toronto, Ont. M5S 1A8, Canada. (George) Department of Medicine, University of Toronto, Toronto, Ont. M5S 1A8, Canada. (Rashid, O'Dowd, George) Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont. M5S 1A8, Canada. Country of Publication United Kingdom Title Neuronal Gq/11-coupled dopamine receptors: an uncharted role for dopamine. Source Trends in Pharmacological Sciences. 28(11)(pp 551-555), 2007. Date of Publication: Nov 2007. Abstract There is strong evidence for the existence of Gq/11-coupled dopamine receptors in the brain but the mechanism by which dopamine signaling activates Gq/11, or its roles in neuronal function, are only just beginning to be understood. The importance of such a pathway is underlined by putative links between dopamine-regulated phosphoinositide signaling and several central nervous system disorders that include schizophrenia, addiction and Parkinson's disease. copyright 2007 Elsevier Ltd. All rights reserved. ISSN 0165-6147 Publication Type Journal: Article Journal Name Trends in Pharmacological Sciences Volume 28 Issue Part 11 Page 551-555 Year of Publication 2007 Date of Publication Nov 2007 NEURO 2007 <894> Database EMBASE Accession Number 2007544002 Authors Zammit S. Spurlock G. Williams H. Norton N. Williams N. O'Donovan M.C. Owen M.J. Institution (Zammit, Spurlock, Williams, Norton, Williams, O'Donovan, Owen) Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom. (Zammit) Department of Psychological Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom. Country of Publication United Kingdom Title Genotype effects of CHRNA7, CNRI and COMT in schizophrenia: Interactions with tobacco and cannabis use. Source British Journal of Psychiatry. 191(NOV.)(pp 402-407), 2007. Date of Publication: Nov 2007. Abstract Background: Genetic variations might modify associations between schizophrenia and cannabis or tobacco use. Aims: To examine whether variants within the cannabinoid receptor (CNRI) and alpha<sub>7</sub> nicotinic receptor (CHRNA7) genes are associated with schizophrenia, and whether these effects vary according to cannabis or tobacco use. We also examined a putative interaction between cannabis and Val<sup>158</sup>Met within the catechol-O-methyltransferase gene (COMT). Method: Genotype effects of CHRNA7 and CNRI were studied in a case-control sample of 750 individuals with schizophrenia and 688 controls, with interactions for these genes studied in small subsamples. A case-only design of 493 of the schizophrenia group was used to examine interactions between cannabis use and COMT. Results: There was no evidence of association between schizophrenia and CNRI (OR=0.97, 9596 CI 0.82-1.13) or CHRNA7 (OR=1,07, 95% CI 0.77-1.49) genotypes, or of interactions between tobacco use and CHRNA7, or cannabis use and CNRI or COMT genotypes. Conclusions: Neither CNRI nor CHRNA7 variation appears to alter the risk of schizophrenia. Furthermore, our results do not support the presence of different effects of cannabis use on schizophrenia according to variation within COMT. ISSN 0007-1250 Publication Type Journal: Article Journal Name British Journal of Psychiatry Volume 191 Issue Part NOV. Page 402-407 Year of Publication 2007 Date of Publication Nov 2007 NEURO 2007 <896> Database EMBASE Accession Number 2007528536 Authors Angelucci F. Ricci V. Pomponi M. Conte G. Mathe A.A. Attilio Tonali P. Bria P. Institution (Angelucci, Ricci, Pomponi, Conte, Attilio Tonali, Bria) Institute of Neurology, Institute of Psychiatry, Catholic University, Rome, Italy. (Angelucci, Attilio Tonali) Fondazione Don C. Gnocchi, Rome, Italy. (Angelucci, Mathe) Karolinska Institutet, Clinical Neuroscience, Karolinska University Hospital Huddinge, Stockholm, Sweden. (Angelucci) Institute of Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy. Country of Publication United Kingdom Title Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor. Source Journal of Psychopharmacology. 21(8)(pp 820-825), 2007. Date of Publication: Nov 2007. Abstract Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users. copyright 2007 British Association for Psychopharmacology. ISSN 0269-8811 Publication Type Journal: Article Journal Name Journal of Psychopharmacology Volume 21 Issue Part 8 Page 820-825 Year of Publication 2007 Date of Publication Nov 2007 NEURO (A) 2007 <898> Database EMBASE Accession Number 2007519012 Authors Benturquia N. Le Guen S. Canestrelli C. Lagente V. Apiou G. Roques B.P. Noble F. Institution (Benturquia, Le Guen, Canestrelli, Noble) Universite Paris Descartes, Faculte de Pharmacie, 4 avenue de l'Observatoir, Paris, F-75006, France. (Benturquia, Le Guen, Canestrelli, Noble) INSERM, U705, Paris, F-75006, France. (Benturquia, Le Guen, Canestrelli, Roques, Noble) CNRS, UMR 7157, Paris, F-75006, France. (Lagente, Apiou) Air Liquide-Medical Gases Group, Claude-Delorme Research Centre, Jouy-en-Josas, F-78354, France. Country of Publication United Kingdom Title Specific blockade of morphine- and cocaine-induced reinforcing effects in conditioned place preference by nitrous oxide in mice. Source Neuroscience. 149(3)(pp 477-486), 2007. Date of Publication: 09 Nov 2007. Abstract Nitrous oxide (N<sub>2</sub>O), a pharmacological active gas and an antagonist of Nmethyl-D-aspartic acid receptors, has been reported to be effective in the treatment of alcohol and tobacco withdrawal syndrome. However, the neurobiological bases of N<sub>2</sub>O effects are unknown. The aim of the present studies was to examine the effect of N<sub>2</sub>O on acquisition and expression of morphine- (10 mg/kg; s.c.) and cocaine(20 mg/kg; i.p.) induced conditioned place preference (CPP) in mice. Unbiased place conditioning method was used. Mice were exposed to N<sub>2</sub>O during the conditioning phase (acquisition of CPP) or during postconditioning phase (expression of CPP). The same protocol was used to evaluate the impact of N<sub>2</sub>O on locomotor activity, two-trial recognition task (memory), spontaneous alternation, sucrose consumption (anhedonic state), forced swim (depressive state) and elevated O-maze tests (anxiety state). In all these tests, mice were treated with morphine (10 mg/kg, s.c.) the first day, the following day mice were given saline. This sequence alternated during the next 4 days. Control animals received saline every day. The behavior of animals was evaluated on day 8. N<sub>2</sub>O did not induce CPP but impaired the acquisition of morphine-induced CPP and blocked the expression of cocaine- and morphine-induced CPP. The effects of the gas were long lasting and persist 4 days following the exposure. Moreover no behavioral modifications in tests usually used to investigated emotional state as compared with control mice were observed in animals exposed to N<sub>2</sub>O, ruling out an effect of this gas on attention, anxiety, depression, locomotion and anhedonia. These studies raise the possibility that N<sub>2</sub>O could have a clinical benefit in the management of morphine and cocaine addiction. copyright 2007 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 149 Issue Part 3 Page 477-486 Year of Publication 2007 Date of Publication 09 Nov 2007 NEURO (A) 2007 <900> Database EMBASE Accession Number 2007519003 Authors Benagiano V. Lorusso L. Flace P. Girolamo F. Rizzi A. Sabatini R. Auteri P. Bosco L. Cagiano R. Ambrosi G. Institution (Benagiano, Lorusso, Flace, Girolamo, Rizzi) Department of Human Anatomy and Histology, Medical Faculty, University of Bari Policlinico, 11 Piazza Giulio Cesare, 70124 Bari, Italy. (Sabatini) Department of Obstetrics and Gynecology, Medical Faculty, University of Bari Policlinico, Bari, Italy. (Auteri) Department of Ophthalmology, General Hospital, Matera, Italy. (Bosco) Department of Bioethics, University of Bari, Bari, Italy. (Cagiano, Ambrosi) Department of Pharmacology and Human Physiology, Medical Faculty, University of Bari Policlinico, Bari, Italy. Country of Publication United Kingdom Title Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212-2 or CO on the GABAergic neuronal systems of rat cerebellar cortex. Source Neuroscience. 149(3)(pp 592-601), 2007. Date of Publication: 09 Nov 2007. Abstract The aim of this study was to assess the effects of prenatal exposures to cannabinoids or carbon monoxide (CO) in an animal experimental model reproducing the environmental conditions in which a fetus develops whose mother, during pregnancy, ingests by smoking low doses of cannabinoids or CO. Particular attention was devoted to analyses of the longterm effects of the exposures at the level of the cerebellar cortex, where already during prenatal development the GABAergic neuronal systems may be modulated by both cannabinoids and CO. Three groups of rats were subjected to the following experimental conditions: exposure to cannabinoids by maternal treatment during pregnancy with the cannabinoid CB-1 receptor agonist WIN 55212-2 (WIN) (0.5 mg/kg/day, s.c.); exposure to CO by maternal exposure during pregnancy to CO (75 parts per million, by inhalation); and exposure to WIN+CO at the above doses and means of administration; a fourth group was used as control. The body weight of dams, length of pregnancy, litter size at birth, body weight and postnatal mortality of pups were monitored in order to evaluate possible effects of the exposures on reproduction and on prenatal and postnatal development. In the different groups, the long-term effects of the exposures were studied in adult rats (120-150 days) by light microscopy analyses of the structure of the cerebellar cortex and of the distribution in the cortex of markers of GABAergic neurons, such as GAD and GABA itself. Results. Exposures to WIN or CO did not affect reproduction or prenatal/postnatal development. Moreover, the exposed rats showed no structural alterations of the cerebellar cortex and displayed qualitative distribution patterns of GAD and GABA immunoreactivities similar to those of the controls. However, quantitative analyses indicated significant changes of both of these immunoreactivities: in comparison with the controls, they were significantly increased in WINexposed rats and reduced in CO-exposed rats, but not significantly different in WIN+COexposed rats. The changes were detected in the molecular and Purkinje neuron layers, but not in the granular layer. Prenatal exposures of rats to WIN or CO, at doses that do not affect reproduction, general processes of development and histomorphogenesis of the cerebellar cortex, cause significant changes of GAD and GABA immunoreactivities in some GABAergic neuronal systems of the adult rat cerebellar cortex, indicating selective up-regulation of GABA-mediated neurotransmission as a long-term consequence of chronic prenatal exposures to cannabinoids or CO. Because the changes consist of overexpression or, vice versa, underexpression of these immunoreactivities, functional alterations of opposite types in the GABAergic systems of the cerebellum following exposure to WIN or CO can be postulated, in agreement with the results of behavioral and clinical studies. No changes in immunoreactivities were detected after prenatal exposure to WIN and CO in association. copyright 2007 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 149 Issue Part 3 Page 592-601 Year of Publication 2007 Date of Publication 09 Nov 2007 NEURO 2007 <910> Database EMBASE Accession Number 2007497585 Authors Janero D.R. Makriyannis A. Institution (Janero) Center for Drug Discovery, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, United States. Country of Publication United Kingdom Title Targeted modulators of the endogenous cannabinoid system: Future medications to treat addiction disorders and obesity. Source Current Psychiatry Reports. 9(5)(pp 365-373), 2007. Date of Publication: Oct 2007. Abstract The endogenous endocannabinoid system encompasses a family of natural signaling lipids ("endocannabinoids") functionally related to Delta<sup>9</sup>-tetrahydrocannabinol, the psychoactive ingredient of marijuana (cannabis), along with proteins that modulate the endocannabinoids, including enzymes, transporters, and receptors. The endocannabinoid system's ubiquitous regulatory actions in health and disease underscore its importance to mammalian (patho)physiology and suggest discrete targets through which it may be modulated for therapeutic gain. Medications based on the endocannabinoid system are an important focus of contemporary translational research, particularly with respect to substance abuse and obesity, two prevalent disorders with a pathogenic component of endocannabinoid system hyperactivity. Pressing health care needs have made the rational design of targeted CB1 cannabinoid-receptor modulators a promising route to future medications with significant therapeutic impact against psychobehavioral and metabolic disturbances having a rewardsupported appetitive component. Copyright copyright 2007 by Current Medicine Group LLC. ISSN 1523-3812 Publication Type Journal: Review Journal Name Current Psychiatry Reports Volume 9 Issue Part 5 Page 365-373 Year of Publication 2007 Date of Publication Oct 2007 NEURO 2007 <914> Database EMBASE Accession Number 2007521799 Authors Kauer J.A. Malenka R.C. Institution (Kauer) Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, United States. (Malenka) Nancy Pritzker Laboratory, Department of Psychiatry and Behavioural Sciences, Stanford University School of Medicine, Stanford, CA 94304, United States. Country of Publication United Kingdom Title Synaptic plasticity and addiction. Source Nature Reviews Neuroscience. 8(11)(pp 844-858), 2007. Date of Publication: Nov 2007. Abstract Addiction is caused, in part, by powerful and long-lasting memories of the drug experience. Relapse caused by exposure to cues associated with the drug experience is a major clinical problem that contributes to the persistence of addiction. Here we present the accumulated evidence that drugs of abuse can hijack synaptic plasticity mechanisms in key brain circuits, most importantly in the mesolimbic dopamine system, which is central to reward processing in the brain. Reversing or preventing these drug-induced synaptic modifications may prove beneficial in the treatment of one of society's most intractable health problems. copyright 2007 Nature Publishing Group. ISSN 1471-003X Publication Type Journal: Review Journal Name Nature Reviews Neuroscience Volume 8 Issue Part 11 Page 844-858 Year of Publication 2007 Date of Publication Nov 2007 NEURO 2007 <926> Database EMBASE Accession Number 2007500289 Authors Schumann G. Institution (Schumann) Institute of Psychiatry, NIHR-Biomedical Research Centre 'Mental Health', King's College, London, United Kingdom. Country of Publication United Kingdom Title Okey lecture 2006: Identifying the neurobiological mechanisms of addictive behaviour. Source Addiction. 102(11)(pp 1689-1695), 2007. Date of Publication: Nov 2007. Abstract Introduction: Substance use disorders are extremely costly to the individual and to society, and a substantial proportion of patients do not respond to the therapies offered. To improve existing treatments a better understanding of the neurobiological and genetic basis of addictive behaviour and substance use disorder is warranted. The aim of this lecture is to develop a model of integrated translational addiction research which may result in the establishment of individualized therapeutic approaches for patients with substance use disorders. Methods: The genetic basis of substance use disorders is characterized by a contribution of multiple genes to the clinical phenotype. This genetic complexity is based on poly/oligogenicity and genetic heterogeneity, two parallel mechanisms which are present to varying extents in different substance use disorders. To disentangle the complexity and to identify the genetic and neurobiological basis of addictions an integrated, translational approach involving (functional) genetic analyses, animal behavioural experimentation and neuroimaging studies is proposed. Results: Examples of this approach are provided by describing a line of work which identified the relevance of circadian rhythm genes in regulating alcohol drinking behaviour in animal models and humans, as well as a complementary approach using endophenotypes in human gene-neuroimaging studies where the effect of single and combined genetic variations on processing of aversive emotional stimuli in the limbic system was demonstrated. Discussion: While the combination of genetic, behavioural and neuroimaging analyses are shown to be useful tools to address oligogenicity and genetic heterogeneity in substance use disorders, the clinical relevance of this approach needs to be developed further. Thus, two current major research projects, the European integrated project 'IMAGEN' and the NIHR-Biomedical Research Centre 'Mental Health' in the United Kingdom, which potentially integrate our proposed research strategy with clinically relevant outcomes, will be discussed. copyright 2007 The Author. ISSN 0965-2140 Publication Type Journal: Conference Paper Journal Name Addiction Volume 102 Issue Part 11 Page 1689-1695 Year of Publication 2007 Date of Publication Nov 2007 NEURO (A) 2007 <934> Database EMBASE Accession Number 2007472788 Authors Adams C.L. Lawrence A.J. Institution (Adams) Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, Australia. (Adams, Lawrence) Howard Florey Institute, Parkville, Vic., Australia. (Lawrence) Centre for Neuroscience, University of Melbourne, Vic., Australia. (Lawrence) Howard Florey Institute, Royal Parade, Parkville, Vic. 3010, Australia. Country of Publication United Kingdom Title CGP7930: A positive allosteric modulator of the GABA<sub>B</sub> receptor. Source CNS Drug Reviews. 13(3)(pp 308-316), 2007. Date of Publication: Sep 2007. Abstract CGP7930 (3-(3',5'-Di-tert-butyl-4'-hydroxy)phenyl-2,2- dimethylpropanol) is a positive allosteric modulator of the metabotropic GABA<sub>B</sub> receptor. CGP7930 has been found to modulate the GABA <sub>B</sub> receptor in the open, or high affinity, state increasing agonist affinity for the receptor and signal transduction efficacy following agonist stimulation. The GABA<sub>B</sub> heteromeric subunit B2, involved in signal transduction but not ligand binding, seems to be the site of action of CGP7930 and similar allosteric modulators. When administered alone in naive animals, CGP7930 acts as an anxiolytic in rodents without other overt behavioral effects and has also been demonstrated to reduce selfadministration of nicotine, cocaine, or alcohol in rodents, suggesting that "fine tuning" of the GABA<sub>B</sub> receptor by positive allosteric modulators may be able to regulate abuse of these drugs. Baclofen, the GABA<sub>B</sub> agonist, is currently finding use in treating addiction and various other disorders, but this can result in off-target effects and tolerance. CGP7930 when co-administered with baclofen enhances its potency, which could in theory minimize deleterious effects. Further study of CGP7930 is required, but this compound, and others like it, holds potential in a clinical setting. copyright 2007 The Authors. ISSN 1080-563X Publication Type Journal: Review Journal Name CNS Drug Reviews Volume 13 Issue Part 3 Page 308-316 Year of Publication 2007 Date of Publication Sep 2007 NEURO 2007 <939> Database EMBASE Accession Number 2007410694 Authors Zanger U.M. Klein K. Saussele T. Blievernicht J. Hofmann M.H. Schwab M. Institution (Zanger, Klein, Saussele, Blievernicht, Hofmann, Schwab) Dr Margarete Fischer-Bosch, Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany. (Zanger, Klein, Saussele, Blievernicht, Hofmann, Schwab) University of Tuebingen, Tuebingen, Germany. Country of Publication United Kingdom Title Polymorphic CYP2B6: Molecular mechanisms and emerging clinical significance. Source Pharmacogenomics. 8(7)(pp 743-759), 2007. Date of Publication: Jul 2007. Abstract Polymorphisms in drug-metabolizing enzymes and drug transporters contribute to wide and inheritable variability in drug pharmacokinetics, response and toxicity. One of the less wellstudied human cytochrome P450s is (CYP)2B6, a homologue of the rodent phenobarbitalinducible CYP2B enzymes. Clinically used drug substrates include cytostatics (cyclophosphamide), HIV drugs (efavirenz and nevirapine), antidepressants (bupropion), antimalarials (artemisinin), anesthetics (propofol) and synthetic opioids (methadone). Contrary to the model polymorphisms of CYP2D6 and CYP2C19, which were discovered by adverse drug reactions, pharmacogenetic study of CYP2B6 was initiated by reverse genetics approaches and subsequent functional and clinical studies. With over 100 described SNPs, numerous complex haplotypes and distinct ethnic frequencies, CYP2B6 is one of the most polymorphic CYP genes in humans. In this review, we summarize general biomolecular and pharmacological features and present a detailed up-to-date description of genetic polymorphisms, including a discussion of recent clinical applications of CYP2B6 pharmacogenetics. copyright 2007 Future Medicine Ltd. ISSN 1462-2416 Publication Type Journal: Review Journal Name Pharmacogenomics Volume 8 Issue Part 7 Page 743-759 Year of Publication 2007 Date of Publication Jul 2007 NEURO 2007 <947> Database EMBASE Accession Number 2007478695 Authors Jiao H. Zhang L. Gao F. Lou D. Zhang J. Xu M. Institution (Jiao, Zhang, Gao, Lou, Xu) Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, United States. (Zhang) Division of Neuropathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States. Country of Publication United Kingdom Title Dopamine D<sub>1</sub> and D<sub>3</sub> receptors oppositely regulate NMDAand cocaine-induced MAPK signaling via NMDA receptor phosphorylation. Source Journal of Neurochemistry. 103(2)(pp 840-848), 2007. Date of Publication: Oct 2007. Abstract Development of drug addiction involves complex molecular changes in the CNS. The mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in mediating neuronal activation induced by dopamine, glutamate, and drugs of abuse. We previously showed that dopamine D<sub>1</sub> and D<sub>3</sub> receptors play different roles in regulating cocaine-induced MAPK activation. Although there are functional and physical interactions between dopamine and glutamate receptors, little is known regarding the involvement of D<sub>1</sub> and D<sub>3</sub> receptors in modulating glutamateinduced MAPK activation and underlying mechanisms. In this study, we show that D<sub>1</sub> and D <sub>3</sub> receptors play opposite roles in regulating N-methyl-daspartate (NMDA) -induced activation of extracellular signal-regulated kinase (ERK) in the caudate putamen (CPu). D<sub>3</sub> receptors also inhibit NMDA-induced activation of the c-Jun N-terminal kinase and p38 kinase in the CPu. NMDA-induced activation of the NMDA-receptor R1 subunit (NR1), Ca <sup>2+</sup>/calmodulin-dependent protein kinase II and the cAMP-response element binding protein (CREB), and cocaine-induced CREB activation in the CPu are also oppositely regulated by dopamine D<sub>1</sub> and D<sub>3</sub> receptors. Finally, the blockade of NMDA-receptor reduces cocaine-induced ERK activation, and inhibits phosphorylation of NR1, Ca<sup>2+</sup>/calmodulindependent protein kinase II, and CREB, while inhibiting ERK activation attenuates cocaineinduced CREB phosphorylation in the CPu. These results suggest that dopamine D<sub>1</sub> and D<sub>3</sub> receptors oppositely regulate NMDA- and cocaineinduced MAPK signaling via phosphorylation of NR1. copyright 2007 The Authors. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 103 Issue Part 2 Page 840-848 Year of Publication 2007 Date of Publication Oct 2007 NEURO (A) 2007 <966> Database EMBASE Accession Number 2007470960 Authors Kasahara M. Groenink L. Breuer M. Olivier B. Sarnyai Z. Institution (Kasahara, Sarnyai) Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom. (Groenink, Breuer, Olivier) Department of Psychopharmacology, Utrecht Institute of Pharmaceutical Sciences, University of Utrecht, Netherlands. (Olivier) Department of Psychiatry, Yale University, New Haven, CT, United States. (Sarnyai) Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom. Country of Publication United Kingdom Title Altered behavioural adaptation in mice with neural corticotrophin-releasing factor overexpression. Source Genes, Brain and Behavior. 6(7)(pp 598-607), 2007. Date of Publication: Oct 2007. Abstract Overproduction of corticotrophin-releasing factor (CRF), the major mediator of the stress response, has been linked to anxiety, depression and addiction. CRF excess results in increased arousal, anxiety and altered cognition in rodents. The ability to adapt to a potentially threatening stimulus is crucial for survival, and impaired adaptation may underlie stress-related psychiatric disorders. Therefore, we examined the effects of chronic transgenic neural CRF overproduction on behavioural adaptation to repeated exposure to a non-home cage environment. We report that CRF transgenic mice show impaired adaptation in locomotor response to the novel open field. In contrast to wild-type (WT) mice, anxiety-related behaviour of CRF transgenic mice does not change during repeated exposure to the same environment over the period of 7 days or at retest 1 week later. We found that locomotor response to novelty correlates significantly with total locomotor activity and activity in the centre at the last day of testing and at retest in WT but not in CRF transgenic mice. Mice were divided into low responders and high responders on the basis of their initial locomotor response to novelty. We found that differences in habituation and re-exposure response are related to individual differences in locomotor response to novelty. In summary, these results show that CRF transgenic mice are fundamentally different from WT in their ability to adapt to an environmental stressor. This may be related to individual differences in stress reactivity. These findings have implications for our understanding of the role of CRF overproduction in behavioural maladaptation and stress-related psychiatric disorders. copyright 2006 Blackwell Publishing Ltd. ISSN 1601-1848 Publication Type Journal: Article Journal Name Genes, Brain and Behavior Volume 6 Issue Part 7 Page 598-607 Year of Publication 2007 Date of Publication Oct 2007 NEURO 2007 <978> Database EMBASE Accession Number 2007426676 Authors Dawson K.S. Batchelor J. Meares S. Chapman J. Marosszeky J.E. Institution (Dawson, Batchelor, Meares) Macquarie University, Sydney, NSW, Australia. (Chapman, Marosszeky) Department of Rehabilitation Medicine, Westmead Hospital, Sydney, NSW, Australia. Country of Publication United Kingdom Title Applicability of neural reserve theory in mild traumatic brain injury. Source Brain Injury. 21(9)(pp 943-949), 2007. Date of Publication: Aug 2007. Abstract Objective: The aim of the current study was to examine whether neural reserve influenced the duration of post-traumatic amnesia (PTA) following mild traumatic brain injury (MTBI). Method: The relationship between duration of PTA and both IQ and education was examined in a group of 59 MTBI patients. In addition, the effects of factors that could potentially diminish neural reserve, namely pre-injury hazardous alcohol consumption, pre-injury marijuana use, previous neurological damage, age and post-injury emotional distress on PTA duration were analysed. Results: Significant, negative associations between PTA duration and both IQ and education were revealed. None of the other variables that were examined were significantly related to PTA duration. Conclusion: The findings were interpreted as providing preliminary evidence to suggest that reference to neural reserve may help explain between-subject variability in acute response to MTBI. ISSN 0269-9052 Publication Type Journal: Article Journal NameBrain Injury Volume 21 Issue Part 9 Page 943-949 Year of Publication 2007 Date of Publication Aug 2007 NEURO 2007 <993> Database EMBASE Accession Number 2007426205 Authors Chambers R.A. Bickel W.K. Potenza M.N. Institution (Chambers) Laboratory for Translational Neuroscience of Dual Diagnosis and Development, Institute of Psychiatric Research, Indiana Division of Mental Health and Addiction, 791 Union Drive, Indianapolis, IN 46202, United States. (Bickel) Center for Addiction Research, College of Medicine, Center for the Study of Tobacco, Little Rock, AR, United States. (Potenza) Problem Gambling Clinic at Yale, Women and Addictions Core of Women's Health Research at Yale, Neuroimaging, New Haven, CT, United States. Country of Publication United Kingdom Title A scale-free systems theory of motivation and addiction. Source Neuroscience and Biobehavioral Reviews. 31(7)(pp 1017-1045), 2007. Date of Publication: 2007. Abstract Scale-free organizations, characterized by uneven distributions of linkages between nodal elements, describe the structure and function of many life-based complex systems developing under evolutionary pressures. We explore motivated behavior as a scale-free map toward a comprehensive translational theory of addiction. Motivational and behavioral repertoires are reframed as link and nodal element sets, respectively, comprising a scale-free structure. These sets are generated by semi-independent information-processing streams within cortical-striatal circuits that cooperatively provide decision-making and sequential processing functions necessary for traversing maps of motivational links connecting behavioral nodes. Dopamine modulation of cortical-striatal plasticity serves a central-hierarchical mechanism for survival-adaptive sculpting and development of motivational-behavioral repertoires by guiding a scale-free design. Drug-induced dopamine activity promotes drug taking as a highly connected behavioral hub at the expense of natural-adaptive motivational links and behavioral nodes. Conceptualizing addiction as pathological alteration of scale-free motivational-behavioral repertoires unifies neurobiological, neurocomputational and behavioral research while addressing addiction vulnerability in adolescence and psychiatric illness. This model may inform integrative research in defining more effective prevention and treatment strategies for addiction. copyright 2007 Elsevier Ltd. All rights reserved. ISSN 0149-7634 Publication Type Journal: Review Journal Name Neuroscience and Biobehavioral Reviews Volume 31 Issue Part 7 Page 1017-1045 Year of Publication 2007 Date of Publication 2007 NEURO 2007 <132> Database EMBASE Accession Number 2007297635 Authors Andrade E.C. Krueger D.D. Nairn A.C. Institution (Andrade, Krueger, Nairn) Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06508, United States. (Nairn) Yale University School of Medicine, Yale/NIDA Neuroproteomics Center, New Haven, CT 06508, United States. Country of Publication United Kingdom Title Recent advances in neuroproteomics. Source Current Opinion in Molecular Therapeutics. 9(3)(pp 270-281), 2007. Date of Publication: Jun 2007. Abstract The last few years have seen a rapid growth in the use of proteomic methods to study normal brain function. In addition, such methods have been used to analyze changes in protein expression associated with the onset and progression of neuronal disease. The field of neuroproteomics faces special challenges given the complex cellular and sub-cellular architecture of the central nervous system. This article presents a review of recent progress in studies of neuroproteomics, and highlights the strengths and limitations of current proteomic profiling technologies used in studies of neuronal protein expression. copyright The Thomson Corporation. ISSN 1464-8431 Publication Type Journal: Review Journal Name Current Opinion in Molecular Therapeutics Volume 9 Issue Part 3 Page 270-281 Year of Publication 2007 Date of Publication Jun 2007 NEURO 2007 <145> Database EMBASE Accession Number 2007082336 Authors Di Chiara G. Bassareo V. Institution (Di Chiara, Bassareo) Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. Country of Publication United Kingdom Title Reward system and addiction: what dopamine does and doesn't do. Source Current Opinion in Pharmacology. 7(1)(pp 69-76), 2007. Date of Publication: Feb 2007. Abstract Addictive drugs share with palatable food the property of increasing extracellular dopamine (DA), preferentially in the nucleus accumbens shell rather than in the core. However, by acting directly on the brain, drugs bypass the adaptive mechanisms (habituation) that constrain the responsiveness of accumbens shell DA to food reward, abnormally facilitating Pavlovian incentive learning and promoting the acquisition of abnormal DA-releasing properties by drug conditioned stimuli. Thus, whereas Pavlovian food conditioned stimuli release core but not shell DA, drug conditioned stimuli do the opposite, releasing shell but not core DA. This process, which results in the acquisition of excessive incentive-motivational properties by drug conditioned stimuli, initiates the drug addiction process. Neuroadaptive processes related to the chronic influence of drugs on subcortical DA might secondarily impair the function of prefronto-striatal loops, resulting in impairments in impulse control and decision making that form the basis for the compulsive feature of drug seeking and its relapsing character. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 1471-4892 Publication Type Journal: Review Journal Name Current Opinion in Pharmacology Volume 7 Issue Part 1 Page 69-76 Year of Publication 2007 Date of Publication Feb 2007 NEURO 2007 <146> Database EMBASE Accession Number 2007082331 Authors Girault J.-A. Valjent E. Caboche J. Herve D. Institution (Girault, Valjent, Herve) INSERM, UMR-S536, F-75005 Paris, France. (Girault, Valjent, Caboche, Herve) Universite Pierre et Marie Curie-Paris 6, F-75005 Paris, France. (Girault, Valjent, Herve) Institut du Fer a Moulin, F-75005 Paris, France. (Caboche) CNRS UMR7102, F-75005 Paris, France. Country of Publication United Kingdom Title ERK2: a logical AND gate critical for drug-induced plasticity? Source Current Opinion in Pharmacology. 7(1)(pp 77-85), 2007. Date of Publication: Feb 2007. Abstract Drug addiction results in part from the distortion of dopamine-controlled plasticity, and extracellular signal-regulated kinase (ERK) plays an important role in the underlying molecular mechanisms of this process. ERK is activated by drugs of abuse in a subset of neurons in reward-related brain regions. This activation, necessary for the expression of immediate early genes, depends upon dopamine D1 and glutamate receptors. Blockade of ERK activation prevents long-lasting behavioral changes, including psychomotor sensitization and conditioned place preference. It also interferes with drug craving and drug-associated memory reconsolidation. By contrast, ERK1 mutation enhances the effects of morphine and cocaine. We suggest that the ERK2 pathway acts as a logical AND gate, permissive for plasticity, in neurons on which dopamine-mediated reward signals and glutamate-mediated contextual information converge. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 1471-4892 Publication Type Journal: Review Journal Name Current Opinion in Pharmacology Volume 7 Issue Part 1 Page 77-85 Year of Publication 2007 Date of Publication Feb 2007 NEURO 2007 <150> Database EMBASE Accession Number 2007080116 Authors Ranft A. Kurz J. Becker K. Dodt H.-U. Zieglgansberger W. Rammes G. Kochs E. Eder M. Institution (Ranft, Kurz, Becker, Dodt, Zieglgansberger, Rammes, Eder) Klinische Neuropharmakologie, Max-Planck-Institut fur Psychiatrie, Kraepelinstrasse 2-10, 80804 Munchen, Germany. (Ranft, Kurz, Rammes, Kochs) Klinik fur Anaesthesiologie, Klinikums rechts der Isar der Technischen Universitat Munchen, Ismaninger Str. 22, 81675 Munchen, Germany. Country of Publication United Kingdom Title Nitrous oxide (N<sub>2</sub>O) pre- and postsynaptically attenuates NMDA receptor-mediated neurotransmission in the amygdala. Source Neuropharmacology. 52(3)(pp 716-723), 2007. Date of Publication: Mar 2007. Abstract The gaseous anaesthetic N<sub>2</sub>O displays analgesic, anxiolytic, and amnesic properties and has addictive psychedelic effects. N<sub>2</sub>O can further act as a neuroprotective agent, but may also become neurotoxic under certain conditions. Here, we employed whole-cell patch-clamp techniques in acute brain slices, and electrical afferent and infrared-guided laser stimulation to examine how N<sub>2</sub>O (65%) can affect NMDA receptor (NMDAR)-mediated synaptic transmission to principal neurons (PNs) of the adult murine basolateral amygdala (BLA). The BLA plays a critical role in anaesthetic-induced amnesia, the formation of aversive memories, as well as in fear and addictive behaviour. We evoked NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) in PNs of the BLA (BLA-PNs). We found these currents to be markedly decreased by N<sub>2</sub>O via pre- and postsynaptic actions: Without changing their kinetics and open probability, N<sub>2</sub>O impeded the voltage-dependent channel opening of NMDARs in BLA-PNs and diminished their unitary conductance as estimated by non-stationary fluctuation analysis. In addition, our data speak in favour of a N<sub>2</sub>O-produced reduction in the probability of glutamate release at the synapses generating the NMDAR-EPSCs. It is conceivable that these effects not only contribute to anaesthesia and anxiolysis, but also have bearings on learning and memory as well as excitotoxicity in the amygdala. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Article Journal Name Neuropharmacology Volume 52 Issue Part 3 Page 716-723 Yearr of Publication 2007 Date of Publication Mar 2007 NEURO 2007 <153> Database EMBASE Accession Number 2007073208 Authors Mizuno T. Schmauss C. Rayport S. Institution (Mizuno, Schmauss, Rayport) Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, United States. (Mizuno, Schmauss, Rayport) Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States. Country of Publication United Kingdom Title Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens. Source BMC Neuroscience. 8, 2007. Article Number: 8. Date of Publication: 2007. Abstract Background: In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca<sup>2+</sup> levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy. Results: Presynaptic Ca<sup>2+</sup> rises were differentia lly modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptormediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon. Conclusion: Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of medium-spiny neuron varicosities, the heterogeneous distribution of dopamine receptors on individual varicosities is likely to encode patterns in striatal information processing. copyright 2007 Mizuno et al; licensee BioMed Central Ltd. Publication Type Journal: Article Journal Name BMC Neuroscience Volume 8 Year of Publication 2007 Date of Publication 2007 NEURO 2007 <162> Database EMBASE Accession Number 2007045934 Authors Cecchini M. LoPresti V. Institution (Cecchini, LoPresti) Foundation for Advancements in Science and Education, 4801 Wilshire Boulevard, Suite 215, Los Angeles, CA 90010, United States. Country of Publication United Kingdom Title Drug residues store in the body following cessation of use: Impacts on neuroendocrine balance and behavior - Use of the Hubbard sauna regimen to remove toxins and restore health. Source Medical Hypotheses. 68(4)(pp 868-879), 2007. Date of Publication: 2007. Abstract For decades, scientists have investigated the environmental and human health effects of synthetic chemicals. A growing body of research has illuminated the spectrum of consequences deriving from our reliance these substances and their proliferation in air, water, soil and the food chain. Of particular concern is the fact that residues of many man-made chemicals are now detectible in virtually every person. A key to a chemical's tendency to persist in tissues once it has entered the body is its lipophilicity. Substances that are poorly soluble in water and quite soluble in fat have relatively free access, via lipid-rich cellular membranes, to the cells of all organs including the ability to cross the blood-brain and placental barriers. Substantial data exist demonstrating that in addition to pollutants, drugs and their metabolites dispose to tissues high in fat content, including brain and adipose. While their characteristic lipophilicity permits drugs and medications to reach target tissues, thereby producing therapeutic effects in the present, current perceptions of risk may be ignoring the possibility that adipose accumulations of illicit drugs and pharmaceuticals may lead to future patterns of ill health similar to those associated with exposure to other categories of xenobiotic chemicals. Empirical data are beginning to characterize the myriad regulatory functions of adipose hormones, including roles in cravings, cognitive function, energy level, and inflammation as well as changes in adipose hormone levels associated with drug use. Included in this data are the observation that a rehabilitative treatment intervention introduced by L. Ron Hubbard in 1978 to aid in the broad elimination of chemicals from body stores improves symptoms common to both chemical exposure and drug addiction. The regimen, which includes exercise, sauna bathing, and vitamin and mineral supplementation, is utilized by nearly 70 drug rehabilitation and medical practices in over 20 countries. At present, much more is unknown than is known regarding long-term drug retention and effects. This subject deserves careful evaluation given its potential implications for health and chronic illnesses of poorly defined etiology (such as chronic fatigue syndrome), as well as drug abuse prevention, drug rehabilitation, forensic and legal areas. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 0306-9877 Publication Type Journal: Article Journal Name Medical Hypotheses Volume 68 Issue Part 4 Page 868-879 Year of Publication 2007 Date of Publication 2007 NEURO 2007 <184> Database EMBASE Accession Number 2007030529 Authors Wang J.Q. Fibuch E.E. Mao L. Institution (Wang, Mao) Department of Basic Medical Science, University of Missouri-Kansas City, School of Medicine, Kansas City, MO, United States. (Wang, Fibuch) Department of Anesthesiology, University of Missouri-Kansas City, School of Medicine, 2411 Holmes Street, Kansas City, MO, United States. (Wang) Department of Basic Medical Science, University of Missouri-Kansas City, School of Medicine, 2411 Holmes Street, Kansas City, MO, United States. Country of Publication United Kingdom Title Regulation of mitogen-activated protein kinases by glutamate receptors. Source Journal of Neurochemistry. 100(1)(pp 1-11), 2007. Date of Publication: Jan 2007. Abstract Glutamate receptors regulate gene expression in neurons by activating intracellular signaling cascades that phosphorylate transcription factors within the nucleus. The mitogen-activated protein kinase (MAPK) cascade is one of the best characterized cascades in this regulatory process. The Ca <sup>2+</sup>-permeable ionotropic glutamate receptor, mainly the NMDA receptor subtype, activates MAPKs through a biochemical route involving the Ca <sup>2+</sup>-sensitive Ras-guanine nucleotide releasing factor, Ca <sup>2+</sup>/calmodulin-dependent protein kinase II, and phosphoinositide 3-kinase. The metabotropic glutamate receptor (mGluR), however, activates MAPKs primarily through a Ca<sup>2+</sup>-insensitve pathway involving the transactivation of receptor tyrosine kinases. The adaptor protein Homer also plays a role in this process. As an information superhighway between surface glutamate receptors and transcription factors in the nucleus, active MAPKs phosphorylate specific transcription factors (Elk-1 and CREB), and thereby regulate distinct programs of gene expression. The regulated gene expression contributes to the development of multiple forms of synaptic plasticity related to long-lasting changes in memory function and addictive properties of drugs of abuse. This review, by focusing on new data from recent years, discusses the signaling mechanisms by which different types of glutamate receptors activate MAPKs, features of each MAPK cascade in regulating gene expression, and the importance of glutamate/MAPK-dependent synaptic plasticity in memory and addiction. copyright 2007 The Authors. ISSN 0022-3042 Publication Type Journal: Short Survey Journal Name Journal of Neurochemistry Volume 100 Issue Part 1 Page 1-11 Year of Publication 2007 Date of Publication Jan 2007 NEURO 2007 <185> Database EMBASE Accession Number 2007030501 Authors Maiya R. Ponomarev I. Linse K.D. Harris R.A. Mayfield R.D. Institution (Maiya, Ponomarev, Harris, Mayfield) Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, United States. (Maiya, Ponomarev, Harris) Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology, University of Texas at Austin, Austin, TX, United States. (Linse) Proteomics Core Facility, University of Texas at Austin, Austin, TX, United States. (Mayfield) Waggoner Center for Alcohol and Addiction Research, MBB1.124, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, United States. Country of Publication United Kingdom Title Defining the dopamine transporter proteome by convergent biochemical and in silico analyses. Source Genes, Brain and Behavior. 6(1)(pp 97-106), 2007. Date of Publication: Feb 2007. Abstract Monoamine transporters play a key role in neuronal signaling by mediating reuptake of neurotransmitters from the synapse. The function of the dopamine transporter (DAT), an important member of this family of transporters, is regulated by multiple signaling mechanisms, which result in altered cell surface trafficking of DAT. Protein-protein interactions are likely critical for this mode of transporter regulation. In this study, we identified proteins associated with DAT by immunoprecipitation (IP) followed by mass spectrometry. We identified 20 proteins with diverse cellular functions that can be classified as trafficking proteins, cytoskeletal proteins, ion channels and extracellular matrix-associated proteins. DAT was found to associate with the voltage-gated potassium channel Kv2.1 and synapsin Ib, a protein involved in regulating neurotransmitter release. An in silico analysis provided evidence for common transcriptional regulation of the DAT proteome genes. In summary, this study identified a network of proteins that are primary candidates for functional regulation of the DAT, an important player in mechanisms of mental disorders and drug addiction. copyright 2006 Blackwell Publishing Ltd. ISSN 1601-1848 Publication Type Journal: Article Journal Name Genes, Brain and Behavior Volume 6 Issue Part 1 Page 97-106 Year of Publication 2007 Date of Publication Feb 2007 NEURO 2007 <197> Database EMBASE Accession Number 2007250734 Authors Lau C.G. Zukin R.S. Institution (Lau, Zukin) Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, United States. Country of Publication United Kingdom Title NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Source Nature Reviews Neuroscience. 8(6)(pp 413-426), 2007. Date of Publication: Jun 2007. Abstract The number and subunit composition of synaptic N-methyl-D-aspartate receptors (NMDARs) are not static, but change in a cell- and synapse-specific manner during development and in response to neuronal activity and sensory experience. Neuronal activity drives not only NMDAR synaptic targeting and incorporation, but also receptor retrieval, differential sorting into the endosomal-lysosomal pathway and lateral diffusion between synaptic and extrasynaptic sites. An emerging concept is that activity-dependent, bidirectional regulation of NMDAR trafficking provides a dynamic and potentially powerful mechanism for the regulation of synaptic efficacy and remodelling, which, if dysregulated, can contribute to neuropsychiatric disorders such as cocaine addiction, Alzheimer's disease and schizophrenia. copyright 2007 Nature Publishing Group. ISSN 1471-003X Publication Type Journal: Review Journal Name Nature Reviews Neuroscience Volume 8 Issue Part 6 Page 413-426 Year of Publication 2007 Date of Publication Jun 2007 NEURO 2007 <214> Database EMBASE Accession Number 2007222394 Authors Shoblock J.R. Institution (Shoblock) Johnson and Johnson Pharmaceutical Research and Development, L.L.C., San Diego, CA, United States. (Shoblock) Johnson and Johnson Pharmaceutical R and D, LLC, 3210 Merryfield Row, San Diego, CA, United States. Country of Publication United Kingdom Title The pharmacology of Ro 64-6198, a systemically active, nonpeptide NOP receptor (Opiate Receptor-Like 1, ORL-1) agonist with diverse preclinical therapeutic activity. Source CNS Drug Reviews. 13(1)(pp 107-136), 2007. Date of Publication: Mar 2007. Abstract The NOP receptor (formerly referred to as opiate receptor-like 1, ORL-1, LC132, OP<sub>4</sub>, or NOP<sub>1</sub>) is a G protein-coupled receptor that shares high homology to the classic opioid MOP, DOP, and KOP (mu, delta, and kappa, respectively) receptors and was first cloned in 1994 by several groups. The NOP receptor remained an orphan receptor until 1995, when the endogenous neuropeptide agonist, known as nociceptin or orphanin FQ (N/OFQ) was isolated. Five years later, a group at Hoffmann-La Roche reported on the selective, nonpeptide NOP agonist Ro 64-6198, which became the most extensively published nonpeptide NOP agonist and a valuable pharmacological tool in determining the potential of the NOP receptor as a therapeutic target. Ro 64-6198 is systemically active and achieves high brain penetration. It has subnanomolar affinity for the NOP receptor and is at least 100 times more selective for the NOP receptor over the classic opioid receptors. Ro 64-6198 ranges from partial to full agonist, depending on the assay. Preclinical data indicate that Ro 64-6198 may have broad clinical uses, such as in treating stress and anxiety, addiction, neuropathic pain, cough, and anorexia. This review summarizes the pharmacology and preclinical data of Ro 64-6198. copyright 2007 Blackwell Publishing Inc. ISSN 1080-563X Publication Type Journal: Review Journal Name CNS Drug Reviews Volume 13 Issue Part 1 Page 107-136 Year of Publication 2007 Date of Publication Mar 2007