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