Download RCPsych Literature Search NEURO 2007

NEURO <2>
Database EMBASE
Accession Number 2009290906
Authors Nikolic M.
Institution
(Nikolic) Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial
College London, Du Cane Road, London W12 0NN, United Kingdom.
Country of Publication
United Kingdom
Title
Unravelling the complex role of Cdk5 in the developing cerebral cortex.
Source
Future Neurology. 3(6)(pp 729-743), 2008. Date of Publication: 2008.
Publisher
Future Medicine Ltd.
Abstract
The normal development of the mammalian CNS is entirely dependent on the coordinated
behavior of its cellular components. Particular importance is attributed to the correct
morphology, migration and communication of neurons. Recent years have seen the
identification of many extracellular, cell surface and intracellular signaling molecules that are
important for normal CNS development, consequently triggering huge progress in our
understanding of the complex processes involved. A key molecule to emerge is Cdk5. To
date, Cdk5 has been functionally linked with controlled neuronal morphology, migration,
synaptic function, cognition, drug addiction, neuronal death and neurodegeneration. The
complexity of its function has been confirmed by the ever increasing number of diverse
upstream regulators, protein substrates and biological consequences of altered catalytic
function. The aim of this review is to consolidate recent findings concerning the role of Cdk5
in the developing nervous system, particularly the cerebral cortex, where its importance is
most clearly evidenced. copyright 2008 Future Medicine.
ISSN 1479-6708
Publication Type Journal: Review
Journal Name Future Neurology
Volume 3
Issue Part 6
Page 729-743
Year of Publication 2008
Date of Publication 2008
NEURO <16>
Database EMBASE
Accession Number 2009249808
Authors Nugent F.S. Niehaus J.L. Kauer J.A.
Institution
(Nugent, Niehaus, Kauer) Department of Molecular Pharmacology, Physiology and Biotechnology, Brown
University, Providence, RI, United States.
(Kauer) Department of Molecular Pharmacology, Physiology and Biotechnology and Neuroscience, Brown
University, BioMed Building, 171 Meeting St, Providence, RI 02912, United States.
Country of Publication
United Kingdom
Title
PKG and PKA signaling in LTP at GABAergic synapses.
Source
Neuropsychopharmacology. 34(7)(pp 1829-1842), 2009. Date of Publication: June 2009.
Publisher
Nature Publishing Group
Abstract
Drugs of abuse usurp the mechanisms underlying synaptic plasticity in areas of the brain, a
process that may contribute to the development of addiction. We previously reported that
GABAergic synapses onto dopaminergic neurons in the ventral tegmental area (VTA) exhibit
long-term potentiation (LTP(GABA)) blocked by in vivo exposure to morphine. The
presynaptically maintained LTP requires the retrogradely released nitric oxide (NO) to activate
a presynaptic cGMP signaling cascade. Previous work reported that inhibitory GABA(A)
receptor synapses in the VTA are also potentiated by cAMP. Here, we explored the
interactions between cGMP-dependent (PKG) and cAMP-dependent (PKA) protein kinases in
the regulation of these GABAergic synapses and LTP(GABA). Activation of PKG was required
for NO-cGMP signaling and was also essential for the induction of synaptically elicited
LTP(GABA), but not for its maintenance. Synapses containing GABA(A) receptors were
potentiated by NO-cGMP signaling, whereas synapses containing GABA(B) receptors on the
same cells were not potentiated. Moreover, although the cAMP-PKA system potentiated
GABA(A) synapses, synaptically induced LTP(GABA) was independent of PKA activation.
Surprisingly, however, raising cGMP levels saturated potentiation of these synapses,
precluding further potentiation by cAMP and suggesting a convergent end point for both
signaling pathways in the regulation of GABAergic release. We further found that persistent
GABAergic synaptic modifications observed with in vivo morphine did not involve the
presynaptic cAMP-PKA cascade. Taken together, our data suggest a synapse-specific role
for NO-cGMP-PKG signaling pathway in opioid-induced plasticity of VTA GABA(A) synapses.
copyright 2009 Nature Publishing Group.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 34
Issue Part 7
Page 1829-1842
Year of Publication 2009
Date of Publication June 2009
NEURO (A) <18>
Database EMBASE
Accession Number 2009249818
Authors Olsen C.M. Winder D.G.
Institution
(Olsen, Winder) Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine,
Nashville, TN, United States.
(Olsen, Winder) Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN, United
States.
(Olsen, Winder) JF Kennedy Center for Research on Human Development, Vanderbilt University School of
Medicine, Nashville, TN, United States.
(Winder) Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 724B MRB
1, 23rd and Pierce Avenue S, Nashville, TN 37232-0615, United States.
Country of Publication
United Kingdom
Title
Operant sensation seeking engages similar neural substrates to operant drug seeking
in C57 mice.
Source
Neuropsychopharmacology. 34(7)(pp 1685-1694), 2009. Date of Publication: June 2009.
Publisher
Nature Publishing Group
Abstract
Novelty and sensation seeking have been associated with elevated drug intake in human
and animal studies, suggesting overlap in the circuitry mediating these behaviors. In this
study, we found that C57Bl6J mice readily acquired operant responding for dynamic visual
stimuli, a phenomenon we term operant sensation seeking (OSS). Like operant studies using
other reinforcers, mice responded on fixed and progressive ratio schedules, were resistant to
extinction, and had sustained responding with extended access. We also found that OSS, like
psychostimulant self-administration, is sensitive to disruption of dopamine signaling. Low
doses of the dopamine antagonist cis-flupenthixol increased active lever responding, an effect
reported for psychostimulant self-administration. Additionally, D1-deficient mice failed to
acquire OSS, although they readily acquired lever pressing for food. Finally, we found that
one common measure of novelty seeking, locomotor activity in a novel open field, did not
predict OSS performance. OSS may have predictive validity for screening compounds for use
in the treatment of drug addiction. In addition, we also discuss the potential relevance of this
animal model to the field of behavioral addictions. copyright 2009 Nature Publishing Group.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 34
Issue Part 7
Page 1685-1694
Year of Publication 2009
Date of Publication June 2009
NEURO (A) <22>
Database EMBASE
Accession Number 2009244761
Authors Prakash S. Ambrosio E. Alguacil L.F. del Olmo N.
Institution
(Prakash, Alguacil, del Olmo) Departamento de Farmacologia, Tecnologia y Desarrollo
Farmaceutico, Facultad de Farmacia, Universidad San Pablo CEU, Boadilla del Monte, 28668
Madrid, Spain.
(Ambrosio) Departamento de Psicobiologia, Facultad de Psicologia, UNED, 28040 Madrid,
Spain.
Country of Publication
United Kingdom
Title
Genetic differences in hippocampal synaptic plasticity.
Source
Neuroscience. 161(2)(pp 342-346), 2009. Date of Publication: 30 Jun 2009.
Publisher
Elsevier Ltd
Abstract
Synaptic plasticity is considered a physiological substrate for learning and memory [Lynch
MA (2004) Long-term potentiation and memory. Physiol Rev 84:87-136] that contributes to
maladaptive learning in drug addiction [Schoenbaum G, Roesch MR, Stalnaker TA (2006)
Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci 29:116-124]. Many
studies have revealed that drug addiction has a strong hereditary component [Kosten TA,
Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with
Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69; Uhl GR (2004)
Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions
to understanding addiction as a mnemonic process. Neuropharmacology 47 (Suppl 1):140147], however the contribution of the genetic background to drug-induced changes in synaptic
plasticity has been scarcely studied. The present study reports on an analysis of long-term
potentiation (LTP) and depotentiation in Lewis (LEW) and Fischer-344 (F344) rats, two inbred
rat strains that show different proneness to drugs of abuse and are considered an
experimental model of genetic vulnerability to addiction [Kosten TA, Ambrosio E (2002) HPA
axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344
inbred rats. Psychoneuroendocrinology 27:35-69]. The induction of saturated-LTP was similar
in LEW and F344 rats treated with saline or cocaine. However, only slices from LEW salinetreated rats showed the reversal of LTP; thus, the depotentiation of saturated-LTP was not
observed in cocaine-injected LEW rats and in F344 animals (treated either with cocaine or
saline). These results suggest significant differences in hippocampal synaptic plasticity
between Lewis and Fischer 344 rats. copyright 2009 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 161
Issue Part 2
Page 342-346
Year of Publication 2009
Date of Publication 30 Jun 2009
NEURO <35>
Database EMBASE
Accession Number 2009219374
Authors Leeman R.F. Grant J.E. Potenza M.N.
Institution
(Leeman) Yale University School of Medicine, Substance Abuse Center, CMHC, 34 Park Street, New Haven, CT
06519, United States.
(Grant) Department of Psychiatry, University of Minnesota Medical Center, St Paul, MN, United States.
(Potenza) Department of Psychiatry, Child Study Center, Yale University School of Medicine, New Haven, CT,
United States.
Country of Publication
United Kingdom
Title
Behavioral and neurological foundations for the moral and legal implications of
intoxication, addictive behaviors and disinhibition.
Source
Behavioral Sciences and the Law. 27(2)(pp 237-259), 2009. Date of Publication: 2009.
Publisher
John Wiley and Sons Ltd
Abstract
Disinhibition and addictive behaviors are related and carry moral implications. Both typically
involve diminished consideration of negative consequences, which may result in harm to
oneself or others. Disinhibition may occur on state and trait levels, and addictive substances
may elicit disinhibitory states, particularly when intoxication is reached. Data suggest that trait
disinhibition and addictions may be conceptualized as involving misdirected motivation with
underlying biological bases including genetic factors, alterations in neurotransmitter systems
and differences in regional brain function. The influences of intoxication on the brain share
similarities with cognitive impairments in individuals with chronic substance abuse and those
with trait disinhibition related to frontal lobe injuries. These findings raise questions about
volitional impairment and morality. Although impaired volition related to disinhibition and
addictive behaviors has been studied from multiple perspectives, additional research is
needed to further characterize mechanisms of impairment. Such findings may have important
implications in multiple legal and psychiatric domains. Copyright copyright 2009 John Wiley &
Sons, Ltd.
ISSN 0735-3936
Publication Type Journal: Article
Journal Name Behavioral Sciences and the Law
Volume 27
Issue Part 2
Page 237-259
Year of Publication 2009
Date of Publication 2009
NEURO <62>
Database EMBASE
Accession Number 2009209122
Authors Blum K. Chen A.L.C. Chen T.J. Braverman E.R. Reinking J. Blum S.H. Cassel K. Downs B.W. Waite R.L.
Williams L. Prihoda T.J. Kerner M.M. Palomo T. Comings D.E. Tung H. Rhoades P. Oscar-Berman M.
Institution
(Blum) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem,
NC, United States.
(Chen) Engineering and Management of Advanced Technology, Chang Jung University, Taiwan (Republic of
China).
(Chen, Reinking) Department of Occupational Health and Safety, Chang Jung University, Taiwan (Republic of
China).
(Braverman) Department of Neurosurgery, Weill Cornell College of Medicine, New York, NY, United States.
(Blum, Blum, Cassel) Department of Psychoneurogenetics, Synaptamine, Inc., San Antonio, TX, United States.
(Blum, Downs, Waite, Williams) Deparment of Nutrigenomics, LifeGen, Inc, San Diego, CA, United States.
(Prihoda) Department of Pathology, University of Texas Health Science Center, San Antonio, TX, United States.
(Blum, Braverman, Kerner) Department of Neurological Research, Path Research Foundation, New York, NY,
United States.
(Palomo) Hospital Universitario 12 de Octubre, Madrid, Spain.
(Comings) Carlsbad Science Foundation, Emeritus, City of Hope National Medical Center, Duarte, CA, United
States.
(Tung) University of California, San Diego Medical Center, Neurological Surgery (Brain and Spinal Disorders), San
Diego, CA, United States.
(Rhoades) Central Valley Pain Management and Wellness Modesto, CA, United States.
(Oscar-Berman) Boston University School of Medicine and Boston VAMC, Boston, MA, United States.
Country of Publication
United Kingdom
Title
Activation instead of blocking mesolimbic dopaminergic reward circuitry is a
preferred modality in the long term treatment of reward deficiency syndrome (RDS): A
commentary.
Source
Theoretical Biology and Medical Modelling. 5, 2008. Article Number: 24. Date of
Publication: 2008.
Publisher
BioMed Central Ltd.
Abstract
Background and hypothesis. Based on neurochemical and genetic evidence, we suggest
that both prevention and treatment of multiple addictions, such as dependence to alcohol,
nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should
consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine
receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system
should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so
will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a
paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA
catabolism due to high catabolic genotype of the COMT gene, are predisposed to selfmedicating any substance or behavior that will activate DA release, including alcohol, opiates,
psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute
utilization of these substances and/or stimulatory behaviors induces a feeling of well being.
Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being
resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors,
due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas
a normal or sufficient amount of DA receptors results in low craving behavior. In terms of
preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors
in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist
induce down regulation, experiments in vitro have shown that constant stimulation of the DA
receptor system via a known D2 agonist results in significant proliferation of D2 receptors in
spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback
mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of
D2 receptors. Proposal and conclusion. The authors propose that D2 receptor stimulation can
be accomplished via the use of Synapatmine, a natural but therapeutic nutraceutical
formulation that potentially induces DA release, causing the same induction of D2-directed
mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors
in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model
has been proven in research showing DNA-directed compensatory overexpression (a form of
gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving
behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to
promote long term dopaminergic activation will ultimately lead to a common, safe and
effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance
Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other
reward deficient aberrant behaviors. This concept is further supported by the more
comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger
in the meso-limbic DA system.
Publication Type Journal: Article
Journal Name Theoretical Biology and Medical Modelling
Volume 5
Year of Publication 2008
Date of Publication 2008
NEURO (A) <65>
Database EMBASE
Accession Number 2009196060
Authors Holmes A. Wellman C.L.
Institution
(Holmes) Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute
on Alcoholism and Alcohol Abuse, 5625 Fishers Lane, Room 2N09, Rockville, MD 20852-9411, United States.
(Wellman) Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States.
Country of Publication
United Kingdom
Title
Stress-induced prefrontal reorganization and executive dysfunction in rodents.
Source
Neuroscience and Biobehavioral Reviews. 33(6)(pp 773-783), 2009. Date of Publication:
June 2009.
Publisher
Elsevier Ltd
Abstract
The prefrontal cortex (PFC) mediates a range of higher order 'executive functions' that
subserve the selection and processing of information in such a way that behavior can be
planned, controlled and directed according to shifting environmental demands. Impairment of
executive functions typifies many forms of psychopathology, including schizophrenia, mood
and anxiety disorders and addiction, that are often associated with a history of trauma and
stress. Recent research in animal models demonstrates that exposure to even brief periods of
intense stress is sufficient to cause significant structural remodeling of the principle projection
neurons within the rodent PFC. In parallel, there is growing evidence that stress-induced
alterations in PFC neuronal morphology are associated with deficits in rodent executive
functions such as working memory, attentional set-shifting and cognitive flexibility, as well as
emotional dysregulation in the form of impaired fear extinction. Although the molecular basis
of stress-induced changes in PFC morphology and function are only now being elucidated, an
understanding of these mechanisms could provide important insight into the pathophysiology
of executive dysfunction in neuropsychiatric disease and foster improved strategies for
treatment. copyright 2009.
ISSN 0149-7634
Publication Type Journal: Review
Journal Name Neuroscience and Biobehavioral Reviews
Volume 33
Issue Part 6
Page 773-783
Year of Publication 2009
Date of Publication June 2009
NEURO (A) <68>
Database EMBASE
Accession Number 2009199217
Authors Meyer P.J. Meshul C.K. Phillips T.J.
Institution
(Meshul, Phillips) Veterans Affairs Medical Center Research Service, Oregon Health and Science University,
Portland, OR, United States.
(Meyer, Phillips) Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United
States.
(Meyer, Meshul, Phillips) Behavioral Neuroscience Department, Oregon Health and Science University, Portland,
OR, United States.
(Phillips) VA Medical Center Research Service (R and D 32), 3710 SW US Veterans Hospital Road, Portland, OR
97239, United States.
Country of Publication
United Kingdom
Title
Ethanol- and cocaine-induced locomotion are genetically related to increases in
accumbal dopamine.
Source
Genes, Brain and Behavior. 8(3)(pp 346-355), 2009. Date of Publication: April 2009.
Publisher
Blackwell Publishing Ltd
Abstract
Neuroanatomical research suggests that interactions between dopamine and glutamate
within the mesolimbic dopamine system are involved in both drug-induced locomotor
stimulation and addiction. Therefore, genetically determined differences in the locomotor
responses to ethanol and cocaine may be related to differences in the effects of these drugs
on this system. To test this, we measured drug-induced changes in dopamine and glutamate
within the nucleus accumbens (NAcc), a major target of mesolimbic dopamine neurons, using
in vivo microdialysis in selectively bred FAST and SLOW mouse lines, which were bred for
extreme sensitivity (FAST) and insensitivity (SLOW) to the locomotor stimulant effects of
ethanol. These mice also show a genetically correlated difference in stimulant response to
cocaine (FAST > SLOW). Single injections of ethanol (2 g/kg) or cocaine (40 mg/kg) resulted
in larger increases in dopamine within the NAcc in FAST compared with SLOW mice. There
was no effect of either drug on NAcc glutamate levels. These experiments indicate that
response of the mesolimbic dopamine system is genetically correlated with sensitivity to
ethanol- and cocaine-induced locomotion. Because increased sensitivity to the stimulating
effects of ethanol appears to be associated with greater risk for alcohol abuse, genetically
determined differences in the mesolimbic dopamine response to ethanol may represent a
critical underlying mechanism for increased genetic risk for alcoholism. copyright 2009
Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.
ISSN 1601-1848
Publication Type Journal: Article
Journal Name Genes, Brain and Behavior
Volume 8
Issue Part 3
Page 346-355
Year of Publication 2009
Date of Publication April 2009
NEURO (A) <95>
Database EMBASE
Accession Number 2009169821
Authors Bie B. Zhu W. Pan Z.Z.
Institution
(Bie, Zhu, Pan) Department of Anesthesiology and Pain Medicine, The University of Texas-MD Anderson Cancer
Center, 1515 Holcombe Boulevard, Unit 110, Houston, TX 77030, United States.
Country of Publication
United Kingdom
Title
Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission
and conditioned place preference in central amygdala.
Source
Neuroscience. 160(2)(pp 348-358), 2009. Date of Publication: 05 May 2009.
Publisher
Elsevier Ltd
Abstract
Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related
at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors
play an essential role in drug reward and dependence for many drugs of abuse including
alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely
unknown at present. Previous animal studies using systemic approaches with DOR
antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease,
an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR
inhibition or deletion. In the present study, we used ethanol-conditioned rats to investigate
adaptive DOR function in neurons of the central nucleus of the amygdala (CeA), a key brain
site for alcohol reward and addiction. We found that functional DOR was absent in glutamate
synapses of CeA neurons from control rats, but it emerged and inhibited glutamate synaptic
currents in CeA neurons from rats displaying ethanol-induced behavior of conditioned place
preference (CPP). Analysis of paired-pulse ratios and miniature glutamate synaptic currents
revealed that the recruited DOR was present on glutamatergic presynaptic terminals. Similar
induction of functional DOR was also found on GABA synapses. Furthermore, microinjection
of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo.
These results suggest that repeated alcohol exposure recruits new functional DOR on CeA
glutamate and GABA synapses, which may be involved in the expression or maintenance of
ethanol-induced CPP behavior. copyright 2009 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 160
Issue Part 2
Page 348-358
Year of Publication 2009
Date of Publication 05 May 2009
NEURO <96>
Database EMBASE
Accession Number 2009183026
Authors Chambers C.D. Garavan H. Bellgrove M.A.
Institution
(Chambers) School of Psychology, Cardiff University, United Kingdom.
(Chambers) Institute of Cognitive Neuroscience, University College London, United Kingdom.
(Garavan) Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
(Bellgrove) School of Psychology, University of Queensland, Australia.
Country of Publication
United Kingdom
Title
Insights into the neural basis of response inhibition from cognitive and clinical
neuroscience.
Source
Neuroscience and Biobehavioral Reviews. 33(5)(pp 631-646), 2009. Date of Publication:
May 2009.
Publisher
Elsevier Ltd
Abstract
Neural mechanisms of cognitive control enable us to initiate, coordinate and update
behaviour. Central to successful control is the ability to suppress actions that are no longer
relevant or required. In this article, we review the contribution of cognitive neuroscience,
molecular genetics and clinical investigations to understanding how response inhibition is
mediated in the human brain. In Section 1, we consider insights into the neural basis of
inhibitory control from the effects of neural interference, neural dysfunction, and drug
addiction. In Section 2, we explore the functional specificity of inhibitory mechanisms among a
range of related processes, including response selection, working memory, and attention. In
Section 3, we focus on the contribution of response inhibition to understanding flexible
behaviour, including the effects of learning and individual differences. Finally, in Section 4, we
propose a series of technical and conceptual objectives for future studies addressing the
neural basis of inhibition. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0149-7634
Publication Type Journal: Review
Journal Name Neuroscience and Biobehavioral Reviews
Volume 33
Issue Part 5
Page 631-646
Year of Publication 2009
Date of Publication May 2009
NEURO (A) <102>
Database EMBASE
Accession Number 2009153469
Authors Kokarovtseva L. Jaciw-Zurakiwsky T. Mendizabal Arbocco R. Frantseva M.V. Perez Velazquez J.L.
Institution
(Kokarovtseva, Jaciw-Zurakiwsky, Mendizabal Arbocco, Perez Velazquez) Neuroscience and Mental Health
Programme and Brain, Behaviour Centre, Division of Neurology, 555 University Avenue, Toronto, Ont. M5G1X8,
Canada.
(Perez Velazquez) Department of Paediatrics, Institute of Medical Science, University of Toronto, Toronto, Canada.
(Frantseva) Department of Psychiatry, Centre for Addiction and Mental Health, 259 College Street, Toronto, Ont.
M5T 1R8, Canada.
Country of Publication
United Kingdom
Title
Excitability and gap junction-mediated mechanisms in nucleus accumbens regulate
self-stimulation reward in rats.
Source
Neuroscience. 159(4)(pp 1257-1263), 2009. Date of Publication: 10 Apr 2009.
Publisher
Elsevier Ltd
Abstract
The nucleus accumbens (Acb) is a part of the striatum which integrates information from
cortical and limbic brain structures, and mediates behaviors which reinforce reward. Previous
work has suggested that neuronal synchrony mediated by gap junctions in Acb-related areas
is involved in brain pleasure and reward. In order to gain insight into functional aspects of the
neural information processing at the level of the striatum, we explored the possible role of Acb
gap junctional communication and chemical synapses on reward self-stimulation in rats using
positive reinforcement. Rats were trained to press a lever that caused an electrical current to
be delivered into the hypothalamus, which is recognized to cause pleasure/reward.
Intracerebral infusion into the Acb of the gap junctional blocker carbenoxolone (CBX)
decreased the lever-pressing activity. Considering that the net effect of blocking gap junctions
is a reduced synchronized output of the cellular activities, which at some level represents a
decrease in excitability, two other inhibitors of neuronal excitability, carbamazepine (CBZ) and
tetrodotoxin (TTX), were infused into the Acb and their effects on lever-pressing assessed. All
manipulations that diminished excitability in the Acb resulted in reduced lever-pressing
activity. CBX and TTX were also infused into motor cortex mediating forelimb lever-pressing
with no effect. However, a manipulation that has the net effect of increasing excitation, the
infusion of the opiate antagonist naloxone, also decreased significantly brain self-stimulation.
We conclude that reward behaviors depend to a great extent on both excitability and gap
junction-mediated mechanisms in Acb neuronal networks. Thus, the Acb provides a site for
the study of pleasure/reward, addiction and conscious experience. copyright 2009 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 159
Issue Part 4
Page 1257-1263
Year of Publication 2009
Date of Publication 10 Apr 2009
NEURO <113>
Database EMBASE
Accession Number 2009149092
Authors Philibert R.A. Gunter T.D. Beach S.R.H. Brody G.H. Hollenbeck N. Andersen A. Adams W.
Institution
(Philibert, Gunter, Hollenbeck, Adams) Department of Psychiatry, University of Iowa, Iowa City, IA,
(Philibert) Department of Neuroscience and Genetics Programs, University of Iowa, Iowa City, IA,
(Andersen) Georgetown University, Washington, DC,
(Beach, Brody) University of Georgia, Athens, GA, United States.
(Philibert) Department of Psychiatry, MEB Psychiatry Research/MEB, Lowa City, IA 52242-1000, United States.
Country of Publication
United Kingdom
Title
Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa
Adoption Studies.
Source
Psychiatric Genetics. 19(2)(pp 91-98), 2009. Date of Publication: April 2009.
Publisher
Lippincott Williams and Wilkins
Abstract
Aim A number of studies have shown that genetic variatior at GABRA2 alters vulnerability to
alcohol dependence. The exact identity of the causal variant(s), and the relationship of these
variants to other forms of substance use and behavioral illness is, however, uncertain.
Objective Therefore, we genotyped 516 individuals from the Iowa Adoption Studies, a large
longitudinal case and control adoption study of substance use, at 39 single nucleotide
polymorphisms encompassing the GABRA2 locus and analyzed them with respect to their
lifetime history of three common forms of substance use dependence [alcohol dependence
(AD), nicotine dependence (ND), and cannabis dependence (CD)] in the Iowa Adoption
Studies and relevant exposure variables. Result Using regression analysis, we found
substantial evidence that both GABRA2 genotype and haplotype are significantly related to
vulnerability to AD, ND, and CD, witt the strongest relationships noted with respect to ND.
Consistent with earlier studies suggesting exposure is an important step in the development
of substance use, we found the inclusion of substance exposure data in our analytic models
markedly increased the strength of the genetic associations of GABRA2 haplotype with
substance use. Finally, we report that the genetic effects were markedly more pronounced in
females than in males. Conclusion We conclude that genetic variation at or near the GABRA2
locus significantly affects vulnerability not only to AD, but to other forms of substance use
including ND and CD, and that the effects may be sex dependent. copyright 2009 Wolters
Kluwer Health.
ISSN 0955-8829
Publication Type Journal: Article
Journal Name Psychiatric Genetics
Volume 19
Issue Part 2
Page 91-98
Year of Publication 2009
Date of Publication April 2009
NEURO <121>
Database EMBASE
Accession Number 2009116141
Authors Le Foll B. Gallo A. Strat Y.L. Lu L. Gorwood P.
Institution
(Le Foll, Gallo) Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of
Toronto, Toronto, Canada.
(Lu) National Institute on Drug Dependence, Peking University, Beijing, China.
(Strat, Gorwood) INSERM U675, University Paris VII, Paris, France.
(Le Foll) Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of
Toronto, 33 Russell Street, Toronto M5S 2S1, Canada.
Country of Publication
United Kingdom
Title
Genetics of dopamine receptors and drug addiction: A comprehensive review.
Source
Behavioural Pharmacology. 20(1)(pp 1-17), 2009. Date of Publication: February 2009.
Publisher
Lippincott Williams and Wilkins
Abstract
Drug dependence is a chronic, relapsing disorder in which compulsive drug-seeking and
drug-taking behaviours persist despite serious negative consequences. Addictive substances,
such as opioids, ethanol, psychostimulants and nicotine, induce pleasant states or relieve
distress, effects that contribute to their recreational use. Dopamine is critically involved in drug
addiction processes. However, the role of the various dopaminergic receptor subtypes has
been difficult to delineate. Here, we will review the information collected implicating the
receptors of the D1 family (DRD1 and DRD5) and of the D2 family (DRD2, DRD 3 and DRD4)
in drug addiction. We will summarize the distribution of these receptors in the brain, the
preclinical experiments carried out with pharmacological and transgenic approaches and the
genetic studies carried out linking genetic variants of these receptors to drug addiction
phenotypes. A meta-analysis of the studies carried out evaluating DRD2 and alcohol
dependence is also provided, which indicates a significant association. Overall, this review
indicates that different aspects of the addiction phenotype are critically influenced by
dopaminergic receptors and that variants of those genes seem to influence some addiction
phenotypes in humans. copyright 2009 Wolters Kluwer Health.
ISSN 0955-8810
Publication Type Journal: Review
Journal Name Behavioural Pharmacology
Volume 20
Issue Part 1
Page 1-17
Year of Publication 2009
Date of Publication February 2009
NEURO (GENETICS) <125>
Database EMBASE
Accession Number 2009134310
Authors Li M.D. Burmeister M.
Institution
(Li) Department of Psychiatry and Neurobehavioural Sciences, University of Virginia, 1670 Discovery Drive,
Charlottesville, VA 22911, United States.
(Burmeister) Molecular and Behavioral Neuroscience Institute, Departments of Psychiatry and Human Genetics,
University of Michigan, 109 South Observatory Street, Ann Arbor, MI 48019, United States.
Country of Publication
United Kingdom
Title
New insights into the genetics of addiction.
Source
Nature Reviews Genetics. 10(4)(pp 225-231), 2009. Date of Publication: April 2009.
Publisher
Nature Publishing Group
Abstract
Drug addiction is a common brain disorder that is extremely costly to the individual and to
society. Genetics contributes significantly to vulnerability to this disorder, but identification of
susceptibility genes has been slow. Recent genome-wide linkage and association studies
have implicated several regions and genes in addiction to various substances, including
alcohol and, more recently, tobacco. Current efforts aim not only to replicate these findings in
independent samples but also to determine the functional mechanisms of these genes and
variants. copyright 2009 Macmillan Publishers Limited. All rights reserved.
ISSN 1471-0056
Publication Type Journal: Review
Journal Name Nature Reviews Genetics
Volume 10
Issue Part 4
Page 225-231
Year of Publication 2009
Date of Publication April 2009