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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