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PHARMACOLOGY 2008 / COCAINE 2008 / ALCOHOL 2008 <152>
Database
EMBASE
Accession Number
2008571958
Authors
Suh J.J. Pettinati H.M. Kampman K.M. O'Brien C.P.
Institution
(Suh, Pettinati, Kampman, O'Brien) Center for Studies of Addiction, Department of Psychiatry, University of
Pennsylvania School of Medicine, Philadelphia, PA, United States.
(Suh, Kampman, O'Brien) Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, United States.
(Suh) Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania, 3900 Chestnut St,
Philadelphia, PA 19104, United States.
Country of Publication
United Kingdom
Title
Gender differences in predictors of treatment attrition with high dose naltrexone in
cocaine and alcohol dependence.
Source
American Journal on Addictions. 17(6)(pp 463-468), 2008. Date of Publication: November
2008.
Publisher
Informa Healthcare
Abstract
Recently, we reported that naltrexone at 150 mg/day significantly decreased cocaine and
alcohol use for men but not women with co-occurring cocaine and alcohol dependence. The
present study is an exploratory investigation of predictors that explain the different gender
responses to naltrexone, with a particular focus on differential predictors of treatment attrition.
No significant predictors were associated with treatment discontinuation in men. Women,
however, were more likely to discontinue treatment when reporting severe pre-treatment
psychiatric problems or nausea while in treatment. Further research on the impact of pretreatment and in-treatment gender differences with naltrexone is warranted. Copyright
copyright American Academy of Addiction Psychiatry.
ISSN 1055-0496
Publication Type Journal: Article
Journal Name American Journal on Addictions
Volume 17
Issue Part 6
Page 463-468
Year of Publication 2008
Date of Publication November 2008
COCAINE (A) 2008 <198>
Database EMBASE
Accession Number 2008485173
Authors Briand L.A. Flagel S.B. Garcia-Fuster M.J. Watson S.J. Akil H. Sarter M. Robinson T.E.
Institution
(Briand, Watson, Akil, Sarter, Robinson) Neuroscience Program, University of Michigan, Ann Arbor, MI, United
States.
(Flagel, Garcia-Fuster, Watson, Akil) Molecular and Behavioral Neuroscience Institute, Ann Arbor, MI, United
States.
(Sarter, Robinson) Biopsychology Program, Department of Psychology, University of Michigan, Ann Arbor, MI,
United States.
(Robinson) Biopsychology Program, Department of Psychology, University of Michigan, 530 Church St., Ann Arbor,
MI 48109, United States.
Country of Publication
United Kingdom
Title
Persistent alterations in cognitive function and prefrontal dopamine D2 receptors
following extended, but not limited, access to self-administered cocaine.
Source
Neuropsychopharmacology. 33(12)(pp 2969-2980), 2008. Date of Publication: November
2008.
Publisher
Nature Publishing Group
Abstract
Drug addicts have deficits in frontocortical function and cognition even long after the
discontinuation of drug use. It is not clear, however, whether the cognitive deficits are a
consequence of drug use, or are present prior to drug use, and thus are a potential
predisposing factor for addiction. To determine if self-administration of cocaine is capable of
producing long-lasting alterations in cognition, rats were allowed access to cocaine for either
1 h/day (short access, ShA) or 6 h/day (long access, LgA) for 3 weeks. Between 1 and 30
days after the last self-administration session, we examined performance on a cognitively
demanding test of sustained attention that requires an intact medial prefrontal cortex. The
expression levels of dopamine D1 and D2 receptor mRNA and D2 protein in the prefrontal
cortex were also examined. Early after discontinuation of drug use, LgA (but not ShA) animals
were markedly impaired on the sustained attention task. Although the LgA animals improved
over time, they continued to show a persistent pattern of performance deficits indicative of a
disruption of cognitive flexibility up to 30 days after the discontinuation of drug use. This was
accompanied by a significant decrease in DA D2 (but not D1) mRNA in the medial and orbital
prefrontal cortex, and D2 receptor protein in the medial prefrontal cortex of LgA (but not ShA)
animals. These findings establish that repeated cocaine use is capable of producing
persistent alterations in the prefrontal cortex and in cognitive function, and illustrate the
usefulness of extended access self-administration procedures for studying the neurobiology
of addiction. copyright 2008 Nature Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 33
Issue Part 12
Page 2969-2980
Year of Publication 2008
Date of Publication November 2008
COCAINE (A) 2008 <199>
Database EMBASE
Accession Number 2008485170
Authors Schroeder F.A. Penta K.L. Matevossian A. Jones S.R. Konradi C. Tapper A.R. Akbarian S.
Institution
(Schroeder, Penta, Matevossian, Tapper, Akbarian) Department of Psychiatry, Brudnick Neuropsychiatric Research
Institute, Worcester, MA, United States.
(Schroeder) Program in Neuroscience, University of Massachusetts Graduate School of Biomedical Sciences,
Worcester, MA, United States.
(Jones) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center
Boulevard, Winston-Salem, NC, United States.
(Konradi) Department of Psychiatry, Vanderbilt University, Nashville, TN, United States.
(Akbarian) Department of Psychiatry, University of Massachusetts Medical School, Brudnick Neuropsychiatric
Research Institute, 303 Belmont Street, Worcester, MA 01604, United States.
Country of Publication
United Kingdom
Title
Drug-induced activation of dopamine D1 receptor signaling and inhibition of class I/II
histone deacetylase induce chromatin remodeling in reward circuitry and modulate
cocaine-related behaviors.
Source
Neuropsychopharmacology. 33(12)(pp 2981-2992), 2008. Date of Publication: November
2008.
Publisher
Nature Publishing Group
Abstract
Chromatin remodeling, including histone modification, is involved in stimulant-induced gene
expression and addiction behavior. To further explore the role of dopamine D1 receptor
signaling, we measured cocaine-related locomotor activity and place preference in mice
pretreated for up to 10 days with the D1 agonist SKF82958 and/or the histone deacetylase
inhibitor (HDACi), sodium butyrate. Cotreatment with D1 agonist and HDACi significantly
enhanced cocaine-induced locomotor activity and place preference, in comparison to singledrug regimens. However, butyrate-mediated reward effects were transient and only apparent
within 2 days after the last HDACi treatment. These behavioral changes were associated with
histone modification changes in striatum and ventral midbrain: (1) a generalized increase in
H3 phosphoacetylation in striatal neurons was dependent on activation of D 1 receptors; (2)
H3 deacetylation at promoter sequences of tyrosine hydroxylase (Th) and brain-derived
neurotrophic factor (Bdnf) in ventral midbrain, together with upregulation of the corresponding
gene transcripts after cotreatment with D1 agonist and HDACi. Collectively, these findings
imply that D1 receptor-regulated histone (phospho)acetylation and gene expression in reward
circuitry is differentially regulated in a region-specific manner. Given that the combination of
D1 agonist and HDACi enhances cocaine-related sensitization and reward, the therapeutic
benefits of D1 receptor antagonists and histone acetyl-transferase inhibitors (HATi) warrant
further investigation in experimental models of stimulant abuse. copyright 2008 Nature
Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 33
Issue Part 12
Page 2981-2992
Year of Publication 2008
Date of Publication November 2008
COCAINE 2008 <214>
Database EMBASE
Accession Number 2008460986
Authors Vlachou S. Stamatopoulou F. Nomikos G.G. Panagis G.
Institution
(Vlachou, Stamatopoulou, Panagis) Department of Psychology, School of Social Sciences, University of Crete,
Rethymnon, Crete, Greece.
(Nomikos) Cannasat Therapeutics, Toronto, ON, Canada.
(Panagis) University of Crete, School of Social Sciences, Department of Psychology, 74100 Rethymnon, Crete,
Greece.
Country of Publication
United Kingdom
Title
Enhancement of endocannabinoid neurotransmission through CB1 cannabinoid
receptors counteracts the reinforcing and psychostimulant effects of cocaine.
Source
International Journal of Neuropsychopharmacology. 11(7)(pp 905-923), 2008. Date of
Publication: November 2008.
Publisher
Cambridge University Press
Abstract
Cannabinoids, in contrast to typical drugs of abuse, have been shown to exert complex
effects on behavioural reinforcement and psychomotor function. We have shown that
cannabinoid agonists lack reinforcing/rewarding properties in the intracranial self-stimulation
(ICSS) paradigm and that the CB1 receptor (CB1R) agonist WIN55,212-2 attenuates the
reward-facilitating actions of cocaine. We sought to determine the effects of the
endocannabinoid neurotransmission enhancer AM-404 (1, 3, 10, 30 mg/kg) on the changes in
ICSS threshold and locomotion elicited by cocaine and extend the study of the effects of
WIN55,212-2 (0.3, 1, 3 mg/kg) on cocaine-induced hyperlocomotion. AM-404 did not exhibit
reward-facilitating properties, and actually increased self-stimulation threshold at the highest
dose. Cocaine significantly reduced self-stimulation threshold, without altering maximal rates
of responding. AM-404 (10 mg/kg) attenuated this action of cocaine, an effect which was
reversed by pretreatment with the selective CB1R antagonist SR141716A. WIN55,212-2
decreased locomotion at the two highest doses, an effect that was blocked by SR141716A;
AM-404 had no effect on locomotion. Cocaine caused a significant, dose-dependent increase
in locomotion, which was reduced by WIN55,212-2 and AM-404. SR141716A blocked the
effects of WIN55,212-2 and AM-404 on cocaine-induced hyperlocomotion. SR141716A alone
had no effect on ICSS threshold or locomotion. These results indicate that cannabinoids may
interfere with brain reward systems responsible for the expression of acute
reinforcing/rewarding properties of cocaine, and provide further evidence that the cannabinoid
system could be explored as a potential drug discovery target for the treatment of
psychostimulant addiction and pathological states associated with psychomotor
overexcitability. Copyright copyright 2008 CINP.
ISSN 1461-1457
Publication Type Journal: Article
Journal Name International Journal of Neuropsychopharmacology
Volume 11
Issue Part 7
Page 905-923
Year of Publication 2008
Date of Publication November 2008
COCAINE 2008 <223>
Database EMBASE
Accession Number 2008480093
Authors Chen Q. Xiong X. Lee T.H. Liu Y. Wetsel W.C. Zhang X.
Institution
(Chen, Xiong, Lee, Wetsel, Zhang) Department of Psychiatry and Behavioral Sciences, Duke University Medical
Center, Durham, NC, United States.
(Liu) Department of Surgery, Duke University Medical Center, Durham, NC, United States.
(Wetsel) Department of Cell Biology, Duke University Medical Center, Durham, NC, United States.
(Zhang) Department of Psychiatry and Behavioral Science, Duke University Medical Center, Box 3870, Durham, NC
27710, United States.
Country of Publication
United Kingdom
Title
Neural plasticity and addiction: Integrin-linked kinase and cocaine behavioral
sensitization.
Source
Journal of Neurochemistry. 107(3)(pp 679-689), 2008. Date of Publication: November 2008.
Publisher
Blackwell Publishing Ltd
Abstract
Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of
biochemical molecules in different brain regions. However, which change is actually related to
drug-produced sensitization lacks of accurate clarification. In this study, we investigated the
role of integrin-linked kinase (ILK) in both the induction and expression of cocaine
sensitization. Conditional inhibition of ILK expression was established in the nucleus
accumbens (NAc) core by microinjecting recombinant adeno-associated virus-carrying,
tetracycline-on-regulated small interfering RNA which reversed the chronic cocaine-induced
psychomotor sensitization, as well as the changes in protein kinase B Ser473
phosphorylation, dendritic density, and dendritic spine numbers locally. Importantly, the
reversed psychomotor sensitization did not recover after cessation of the silencing for 8 days.
We also demonstrated that inhibition of ILK expression pre- and during-chronic cocaine
treatments blocked the induction of cocaine psychomotor sensitization and abolished the
stimulant effect of cocaine on ILK expression. In contrast, inhibition of ILK expression in the
NAc core has no significant effect on cocaine-induced stereotypical behaviors. This concludes
that ILK is involved in cocaine sensitization with the earlier induction and later expression
functioning as a kinase to regulate protein kinase B Ser473 phosphorylation and a scaffolding
protein to regulate the reorganization of the NAc spine morphology. copyright 2008 The
Authors.
ISSN 0022-3042
Publication Type Journal: Article
Journal Name Journal of Neurochemistry
Volume 107
Issue Part 3
Page 679-689
Year of Publication 2008
Date of Publication November 2008
COCAINE (A) <270>
Database EMBASE
Accession Number 2008390017
Authors George O. Mandyam C.D. Wee S. Koob G.F.
Institution
(George, Mandyam, Wee, Koob) Committee on the Neurobiology of Addictive Disorders, Scripps Research Institute,
San Diego, CA, United States.
(George) Committee on the Neurobiology of Addictive Disorders, Scripps Research Institute, SP30-2400, 10550
North Torrey Pines Road, San Diego, CA 92037, United States.
Country of Publication
United Kingdom
Title
Extended access to cocaine self-administration produces long-lasting prefrontal
cortex-dependent working memory impairments.
Source
Neuropsychopharmacology. 33(10)(pp 2474-2482), 2008. Date of Publication: September 2008.
Publisher
Nature Publishing Group
Abstract
Humans with drug addiction exhibit compulsive drug-seeking associated with impairment of
prefrontal cortex cognitive function. Whether prefrontal cortex dysfunction is a consequence
of chronic drug exposure, or mediates the transition from drug use to drug dependence, is
unknown. The current study investigates whether a history of escalated vs controlled cocaine
intake is associated with specific working memory impairments, and long-lasting alterations of
the dorsomedial prefrontal cortex and orbitofrontal cortex in rats. Working memory was
assessed in rats with a history of extended (6 h per session) or limited (1 h per session)
access to cocaine (0.5 mg/kg per injection), 3-17 days after the last self-administration
session, using a delayed nonmatching-to-sample task. The density of neurons,
oligodendrocytes, and astrocytes was quantified in the dorsomedial prefrontal cortex and
orbitofrontal prefrontal cortex 2 months after the last self-administration session. Working
memory impairments were observed after a history of chronic and escalated cocaine intake,
but not after repeated limited access to cocaine. Moreover, working memory impairments
were correlated with a decreased density of neurons and oligodendrocytes but not astrocytes
in the dorsomedial prefrontal cortex, and with a decreased density of oligodendrocytes in the
orbitofrontal cortex. Considering the role of the prefrontal cortex in goal-directed behavior, the
prefrontal cortex dysfunctions observed here may exacerbate the loss of control associated
with increased drug use and facilitate the progression to drug addiction. copyright 2008
Nature Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 33
Issue Part 10
Page 2474-2482
Year of Publication 2008
Date of Publication September 2008
COCAINE 2008 <288>
Database EMBASE
Accession Number 2008422570
Authors Fairbairn C.E. Dundon W.D. Xie H. Plebani J.G. Kampman K.M. Lynch K.G.
Institution
(Fairbairn, Dundon, Xie, Plebani, Kampman, Lynch) Department of Psychiatry, University of Pennsylvania School of
Medicine, Philadelphia, PA, United States.
(Dundon) University of Pennsylvania Treatment Research Center, 3900 Chestnut St, Philadelphia, PA 19104,
United States.
Country of Publication
United Kingdom
Title
Study blinding and correlations between perceived group assignment and outcome in
a cocaine pharmacotherapy trial.
Source
American Journal on Addictions. 17(5)(pp 387-391), 2008. Date of Publication: September
2008.
Publisher
Informa Healthcare
Abstract
While much research has suggested that the integrity of the blind is compromised in
psychotropic drug trials, little research has been conducted on blinding in substance abuse
trials. The current study examines the integrity of the blind in an outpatient pharmacotherapy
trial investigating the effectiveness of amantadine and propranolol in treating cocaine
addiction. Results suggest that neither nurses (N = 174, kappa = 0.08, p = 0.22) nor
participants (N = 163, kappa = 0.09, p = 0.26) could accurately predict treatment assignment.
Furthermore, nurses' perceptions of treatment assignment were significantly related to trial
completion, medication compliance, and cocaine use - results that may have training
implications for medical personnel. Copyright copyright American Academy of Addiction
Psychiatry.
ISSN 1055-0496
Publication Type Journal: Article
Journal Name American Journal on Addictions
Volume 17
Issue Part 5
Page 387-391
Year of Publication 2008
Date of Publication September 2008
COCAINE 2008 <297>
Database EMBASE
Accession Number 2008384509
Authors Numa R. Kohen R. Poltyrev T. Yaka R.
Institution
(Numa, Poltyrev, Yaka) Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Jerusalem, 91120,
Israel.
(Numa, Kohen) Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Jerusalem, 91120, Israel.
Country of Publication
United Kingdom
Title
Tempol diminishes cocaine-induced oxidative damage and attenuates the
development and expression of behavioral sensitization.
Source
Neuroscience. 155(3)(pp 649-658), 2008. Date of Publication: 26 Aug 2008.
Publisher
Elsevier Ltd
Abstract
A variety of mechanisms has been suggested for cocaine toxicity, including the possibility
that cocaine induces an increase in oxidative stress (OS) due to excessive oxidation of
dopamine (e.g. dopamine quinine), or by redox cycling of cocaine oxidized metabolites.
However, the association between oxidative status in the brain and cocaine induced-behavior
is poorly understood. Therefore, we examined the ability of the unique antioxidant tempol to
attenuate cocaine-induced oxidative damage and behavioral response. Acute cocaine
treatment significantly elevated OS markers in prefrontal cortex (PFC) and nucleus
accumbens (NAc) in rats, both in slices and following a single cocaine injection, which
corresponded with a decrease in total antioxidant capacity (TAC). Tempol, at the optimal
concentration we determined that was needed to observe an antioxidant non-toxic effect in
vitro (1 mM) and in vivo (200 mg/kg), completely abolished the elevation of OS markers and
prevented the reduction in TAC in these areas. Importantly, tempol injections, at a dose that
does not affect the basal levels of locomotor activity, attenuated both the development and
expression of cocaine-induced locomotor sensitization. Finally, in cocaine-sensitized animals,
tempol prevented the elevation of OS markers in both PFC and NAc. Our findings suggest
that oxidation of specific sites in the brain reward system by cocaine is accompanied with
behavioral changes. Tempol has a neuro-protective effect against cocaine toxicity in these
regions, and it may be beneficial in the treatment of cocaine addiction. copyright 2008 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 155
Issue Part 3
Page 649-658
Year of Publication 2008
Date of Publication 26 Aug 2008
COCAINE (A) <311>
Database EMBASE
Accession Number 2008384003
Authors Bailey A. Metaxas A. Yoo J.H. McGee T. Kitchen I.
Institution
(Bailey, Metaxas, Yoo, McGee, Kitchen) Faculty of Health and Medical Sciences, AY Building, University of Surrey,
Guildford, Surrey GU2 7XH, United Kingdom.
Country of Publication
United Kingdom
Title
Decrease of D2 receptor binding but increase in D 2-stimulated G-protein activation,
dopamine transporter binding and behavioural sensitization in brains of mice treated
with a chronic escalating dose 'binge' cocaine administration paradigm.
Source
European Journal of Neuroscience. 28(4)(pp 759-770), 2008. Date of Publication: August
2008.
Publisher
Blackwell Publishing Ltd
Abstract
Understanding the neurobiology of the transition from initial drug use to excessive drug use
has been a challenge in drug addiction. We examined the effect of chronic 'binge' escalating
dose cocaine administration, which mimics human compulsive drug use, on behavioural
responses and the dopaminergic system of mice and compared it with a chronic steady dose
(3 x 15 mg/;kg/;day) 'binge' cocaine administration paradigm. Male C57BL/;6J mice were
injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and
stereotypy activity were measured and quantitative autoradiographic mapping of D1 and D2
receptors, dopamine transporters and D 2-stimulated [35S]GTPgammaS binding was
performed in the brains of mice treated with this escalating and steady dose paradigm. An
initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase
in the duration of the locomotor effect of cocaine was observed in the escalating but not the
steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in
cocaine-induced stereotypy score was observed from 3 x 20 to 3 x 25 mg/;kg/;day cocaine.
There was a significant decrease in D2 receptor density, but an increase in D2-stimulated Gprotein activity and dopamine transporter density in the striatum of cocaine-treated mice,
which was not observed in our steady dose paradigm. Our results document that chronic
'binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical
changes in the dopaminergic system, which might underlie the transition from drug use to
compulsive drug use associated with addiction, which is a process of escalation. copyright
The Authors (2008).
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 28
Issue Part 4
Page 759-770
Year of Publication 2008
Date of Publication August 2008
COCAINE 2008 <320>
Database EMBASE
Accession Number 2008299383
Authors Frankel P.S. Alburges M.E. Bush L. Hanson G.R. Kish S.J.
Institution
(Frankel, Alburges, Bush, Hanson) Department of Pharmacology and Toxicology, University of Utah, Salt Lake City,
UT, United States.
(Kish) Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ont. M5T
1R8, Canada.
Country of Publication
United Kingdom
Title
Striatal and ventral pallidum dynorphin concentrations are markedly increased in
human chronic cocaine users.
Source
Neuropharmacology. 55(1)(pp 41-46), 2008. Date of Publication: July 2008.
Publisher
Elsevier Ltd
Abstract
Interest in development of therapeutics targeting brain neuropeptide systems for treatment
of cocaine addiction (e.g., kappa opioid agonists) is based on animal data showing
interactions between the neuropeptides, brain dopamine, and cocaine. In this autopsied brain
study, our major objective was to establish by radioimmunoassay whether levels of dynorphin
and other neuropeptides (e.g., metenkephalin, neurotensin and substance P) are increased in
the dopamine-rich caudate, putamen, and nucleus accumbens of human chronic cocaine
users (n = 12) vs. matched control subjects (n = 17) as predicted by animal findings. Changes
were limited to markedly increased dynorphin immunoreactivity in caudate (+92%), decreased
caudate neurotensin (-49%), and a trend for increased dynorphin (+75%) in putamen. In other
examined subcortical/cerebral cortical areas dynorphin levels were normal with the striking
exception of the ventral pallidum (+346%), whereas cerebral cortical metenkephalin levels
were generally decreased and neurotensin variably changed. Our finding that, in
contradistinction to animal data, the other striatal neuropeptides were not increased in human
cocaine users could be explained by differences in pattern and contingency between human
drug users and the animal models. However, the human dynorphin observations parallel well
animal findings and suggest that the dynorphin system is upregulated, manifested as elevated
neuropeptide levels, after chronic drug exposure in striatum and ventral pallidum. Our
postmortem brain data suggest involvement of striatal dynorphin systems in human cocaine
users and should add to the interest in the testing of new dynorphin-related therapeutics for
the treatment of cocaine addiction. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Article
Journal Name Neuropharmacology
Volume 55
Issue Part 1
Page 41-46
Year of Publication 2008
Date of Publication July 2008
COCAINE (A) 2008 <340>
Database EMBASE
Accession Number 2008375558
Authors Tropea T.F. Kosofsky B.E. Rajadhyaksha A.M.
Institution
(Rajadhyaksha) Weill Medical College of Cornell University, Box 91, 1300 York Avenue, New York, NY 10021,
United States.
(Tropea, Kosofsky, Rajadhyaksha) Department of Pediatrics, New York Presbyterian Hospital, Weill Medical
College of Cornell University, New York, NY, United States.
(Tropea) University of New England, College of Osteopathic Medicine, Biddeford, ME, United States.
(Kosofsky, Rajadhyaksha) Department of Neurology and Neuroscience, Weill Medical College of Cornell University,
New York, NY, United States.
Country of Publication
United Kingdom
Title
Enhanced CREB and DARPP-32 phosphorylation in the nucleus accumbens and
CREB, ERK, and GluR1 phosphorylation in the dorsal hippocampus is associated with
cocaine-conditioned place preference behavior.
Source
Journal of Neurochemistry. 106(4)(pp 1780-1790), 2008. Date of Publication: August 2008.
Publisher
Blackwell Publishing Ltd
Abstract
Environment-induced relapse is a major concern in drug addiction because of the strong
associations formed between drug reward and environment. Cocaine-conditioned place
preference is an ideal experimental tool to examine adaptations in the molecular pathways
that are activated upon re-exposure to an environment previously paired with drug reward. To
better understand the mechanism of cocaine-conditioned place preference we have used
western blot analysis to examine changes in phosphorylation of cAMP-response element
binding protein (CREB), dopamine- and cyclic AMP-regulated phosphoprotein 32 (DARPP32), extracellular signal-regulated kinase (ERK) and GluR1, key molecular substrates altered
by cocaine, in the nucleus accumbens (NAc) and dorsal hippocampus (DHC) of C57BL/6
mice. Our studies revealed that re-exposing mice to an environment in which they were
previously given cocaine resulted in increased levels of Ser133 phospho-CREB and Thr34
phospho-DARPP-32 with a corresponding decrease in Thr75 phospho-DARPP-32 in the NAc.
In DHC there were increased levels of phospho-CREB, Thr183/Tyr185 phospho-ERK, and
Ser845 phospho-GluR1. These data suggest that the formation of contextual drug reward
associations involves recruitment of the DHC-NAc circuit with activation of the DARPP32/CREB pathway in the NAc and the ERK/CREB pathway in the DHC. copyright 2008 The
Authors.
ISSN 0022-3042
Publication Type Journal: Article
Journal Name Journal of Neurochemistry
Volume 106
Issue Part 4
Page 1780-1790
Year of Publication 2008
Date of Publication August 2008
COCAINE (A) 2008 <408>
Database EMBASE
Accession Number 2008320629
Authors Conrad K.L. Tseng K.Y. Uejima J.L. Reimers J.M. Heng L.-J. Shaham Y. Marinelli M. Wolf M.E.
Institution
(Conrad, Reimers, Wolf) Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North
Chicago, IL 60064, United States.
(Tseng, Heng, Marinelli) Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of
Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States.
(Uejima, Shaham) Behavioral Neuroscience Branch, IRP/NIDA/NIH, 251 Bayview Boulevard, Baltimore, MD 21224,
United States.
Country of Publication
United Kingdom
Title
Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of
cocaine craving.
Source
Nature. 454(7200)(pp 118-121), 2008. Date of Publication: 03 Jul 2008.
Publisher
Nature Publishing Group
Abstract
Relapse to cocaine use after prolonged abstinence is an important clinical problem. This
relapse is often induced by exposure to cues associated with cocaine use. To account for the
persistent propensity for relapse, it has been suggested that cue-induced cocaine craving
increases over the first several weeks of abstinence and remains high for extended periods.
We and others identified an analogous phenomenon in rats that was termed 'incubation of
cocaine craving': time-dependent increases in cue-induced cocaine-seeking over the first
months after withdrawal from self-administered cocaine. Cocaine-seeking requires the
activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number
of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from
cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor
2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine
craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for
drug development for the treatment of cocaine addiction. We propose that after prolonged
withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the
higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of
accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and
relapse. copyright2008 Macmillan Publishers Limited. All rights reserved.
ISSN 0028-0836
Publication Type Journal: Article
Journal Name Nature
Volume 454
Issue Part 7200
Page 118-121
Year of Publication 2008
Date of Publication 03 Jul 2008
COCAINE 2008 <411>
Database EMBASE
Accession Number 2008367360
Authors Overton P.G. Devonshire I.M.
Institution
(Overton) Department of Psychology, University of Sheffield, Western Bank, Sheffield, S10 2TP, United Kingdom.
(Devonshire) Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom.
Country of Publication
United Kingdom
Title
Cocaine facilitates craving via an action on sensory processing.
Source
Bioscience Hypotheses. 1(2)(pp 70-77), 2008. Date of Publication: 2008.
Publisher
Elsevier Ltd
Abstract
Sensory systems play an important role in cocaine addiction, perhaps most clearly
demonstrated when stimuli ('cues') associated via classical conditioning with the effects of the
drug, trigger craving and relapse. It has been shown in previous studies that administration of
cocaine can enhance evoked responses in the primary sensory cortex of experimental
animals. Given that the speed of learning in classical conditioning is affected by the intensity
of the conditioned stimulus (CS), and that cocaine enhances the neural representation of
sensory stimuli in the primary sensory cortex in a manner similar to an increase in intensity,
we hypothesise that cue-induced craving in human addicts is facilitated by the drug. In short,
cocaine speeds the process that leads to craving. This hypothesis is supported by the fact
that cocaine enhances sensory responses in humans and leads to an improvement in
attention (the putative intermediary between enhanced sensory responses and facilitated
learning). Furthermore, cocaine affects neural loci which are known to play a role in learning
and facilitates classical conditioning when present during acquisition. In addition, related
drugs like d-amphetamine and ecstasy (which themselves produce craving) affect sensory
processing and attention, and in the case of d-amphetamine facilitate human learning. It is
therefore possible that cocaine itself plays a - previously under-appreciated - role in the
formation of associations between drug and drug-related environmental cues by enhancing
primary sensory responses. A corollary of this is that, as with other intense CSs, the
established association may be particularly resistant to extinction, potentially explaining why
cues continue to elicit craving months or even years after the last cocaine use. copyright 2008
Elsevier Ltd. All rights reserved.
ISSN 1756-2392
Publication Type Journal: Article
Journal Name Bioscience Hypotheses
Volume 1
Issue Part 2
Page 70-77
Year of Publication 2008
Date of Publication 2008
COCAINE 2008 <428>
Database EMBASE
Accession Number 2008289000
Authors Williams M.J. Adinoff B.
Institution
(Williams, Adinoff) Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United
States.
(Adinoff) Mental Health Service, VA North Texas Health Care System, Dallas, TX, United States.
(Williams) Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd,
Dallas, TX 75390-8564, United States.
Country of Publication
United Kingdom
Title
The role of acetylcholine in cocaine addiction.
Source
Neuropsychopharmacology. 33(8)(pp 1779-1797), 2008. Date of Publication: July 2008.
Publisher
Nature Publishing Group
Abstract
Central nervous system cholinergic neurons arise from several discrete sources, project to
multiple brain regions, and exert specific effects on reward, learning, and memory. These
processes are critical for the development and persistence of addictive disorders. Although
other neurotransmitters, including dopamine, glutamate, and serotonin, have been the
primary focus of drug research to date, a growing preclinical literature reveals a critical role of
acetylcholine (ACh) in the experience and progression of drug use. This review will present
and integrate the findings regarding the role of ACh in drug dependence, with a primary focus
on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate
reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine
administration produces neuroadaptive changes in the striatum. ACh is further involved in the
acquisition of conditional associations that underlie cocaine self-administration and contextdependent sensitization, the acquisition of associations in conditioned learning, and drug
procurement through its effects on arousal and attention. Long-term cocaine use may induce
neuronal alterations in the brain that affect the ACh system and impair executive function,
possibly contributing to the disruptions in decision making that characterize this population.
These primarily preclinical studies suggest that ACh exerts a myriad of effects on the
addictive process and that persistent changes to the ACh system following chronic drug use
may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a
potential target for pharmacological treatment interventions in cocaine-addicted subjects.
However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor
subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of
the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation
will be required to impact substance use in the clinical population. copyright 2008 Nature
Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Review
Journal Name Neuropsychopharmacology
Volume 33
Issue Part 8
Page 1779-1797
Year of Publication 2008
Date of Publication July 2008
COCAINE (A) 2008 <430>
Database EMBASE
Accession Number 2008283779
Authors Mitrano D.A. Arnold C. Smith Y.
Institution
(Mitrano, Arnold, Smith) Yerkes National Primate Research Center, Emory University, 954 Gatewood Road
Northeast, Atlanta, GA 30329, United States.
(Mitrano) Molecular and Systems Pharmacology Graduate Program, Emory University, Atlanta, GA 30322, United
States.
(Smith) Department of Neurology, Woodruff Memorial Research Center Emory University, Suite 6000, 1639 Pierce
Drive, Atlanta, GA 30322, United States.
Country of Publication
United Kingdom
Title
Subcellular and subsynaptic localization of group I metabotropic glutamate receptors
in the nucleus accumbens of cocaine-treated rats.
Source
Neuroscience. 154(2)(pp 653-666), 2008. Date of Publication: 23 Jun 2008.
Publisher
Elsevier Ltd
Abstract
There is significant pharmacological and behavioral evidence that group I metabotropic
glutamate receptors (mGluR1a and mGluR5) in the nucleus accumbens play an important
role in the neurochemical and pathophysiological mechanisms that underlie addiction to
psychostimulants. To further address this issue, we undertook a detailed ultrastructural
analysis to characterize changes in the subcellular and subsynaptic localization of mGluR1a
and mGluR5 in the core and shell of nucleus accumbens following acute or chronic cocaine
administration in rats. After a single cocaine injection (30 mg/kg) and 45 min withdrawal, there
was a significant decrease in the proportion of plasma membrane-bound mGluR1a in
accumbens shell dendrites. Similarly, the proportion of plasma membrane-bound mGluR1a
was decreased in large dendrites of accumbens core neurons following chronic cocaine
exposure (i.e. 1-week treatment followed by 3-week withdrawal). However, neither acute nor
chronic cocaine treatments induced significant change in the localization of mGluR5 in
accumbens core and shell, which is in contrast with the significant reduction of plasma
membrane-bound mGluR1a and mGluR5 induced by local intra-accumbens administration of
the group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG). In conclusion, these
findings demonstrate that cocaine-induced glutamate imbalance has modest effects on the
trafficking of group I mGluRs in the nucleus accumbens. These results provide valuable
information on the neuroadaptive mechanisms of accumbens group I mGluRs in response to
cocaine administration. copyright 2008 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 154
Issue Part 2
Page 653-666
Year of Publication 2008
Date of Publication 23 Jun 2008
COCAINE 2008 <434>
Database EMBASE
Accession Number 2008306801
Authors Worley M. Gallop R. Gibbons M.B.C. Ring-Kurtz S. Present J. Weiss R.D. Crits-Christoph P.
Institution
(Worley, Gibbons, Ring-Kurtz, Present, Crits-Christoph) Department of Psychiatry, University of Pennsylvania,
Philadelphia, PA, United States.
(Gallop) Department of Mathematics, West Chester University, West Chester, PA, United States.
(Weiss) McLean Hospital, Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
(Crits-Christoph) 3535 Market St., Philadelphia, PA 19104, United States.
Country of Publication
United Kingdom
Title
Additional treatment services in a cocaine treatment study: Level of services obtained
and impact on outcome.
Source
American Journal on Addictions. 17(3)(pp 209-217), 2008. Date of Publication: May 2008.
Publisher
Informa Healthcare
Abstract
The objective of this study was to examine the level of additional treatment services
obtained by patients enrolled in the NIDA Cocaine Collaborative Study, a multi-center efficacy
trial of four treatments for cocaine dependence, and to determine whether these services
impact treatment outcome. Cocaine-dependent patients (N = 487) were recruited at five sites
and randomly assigned to six months of one of four psychosocial treatments. Assessments
were made at baseline, monthly during treatment, and at follow-ups at 9, 12, 15, and 18
months post-randomization. On average, patients received little or no additional treatment
services during active treatment (first six months), but the rate of obtaining most services
increased during the follow-up phase (month 7 to 18). In general, the treatment groups did not
differ in the rates of obtaining non-protocol services. For all treatment groups, patients with
greater psychiatric severity received more medical and psychiatric services during active
treatment and follow-up. Use of treatment services was unrelated to drug use outcomes
during active treatment. However, during the follow-up period, increased use of psychiatric
medication, twelve-step attendance, and twelve-step participation was related to less drug
use. The results suggest that during uncontrolled follow-up phases, additional non-protocol
services may potentially confound the interpretation of treatment group comparisons in drug
use outcomes. Copyright copyright American Academy of Addiction Psychiatry.
ISSN 1055-0496
Publication Type Journal: Article
Journal Name American Journal on Addictions
Volume 17
Issue Part 3
Page 209-217
Year of Publication 2008
Date of Publication May 2008
COCAINE (A) 2008 <471>
Database EMBASE
Accession Number 2008246711
Authors Zhou Y. Cui C.-L. Schlussman S.D. Choi J.C. Ho A. Han J.-S. Kreek M.J.
Institution
(Zhou, Schlussman, Choi, Ho, Kreek) Laboratory of the Biology of Addictive Diseases, The Rockefeller University,
1230 York Avenue, New York, NY 10065, United States.
(Cui, Han) Bio-organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street,
Belmont, MA 02478, United States.
(Cui, Han, Kreek) Neuroscience Research Institute, Peking University, 38 Xueyuan Road, Beijing, 100083, China.
Country of Publication
United Kingdom
Title
Effects of cocaine place conditioning, chronic escalating-dose "binge" pattern
cocaine administration and acute withdrawal on orexin/hypocretin and
preprodynorphin gene expressions in lateral hypothalamus of Fischer and SpragueDawley rats.
Source
Neuroscience. 153(4)(pp 1225-1234), 2008. Date of Publication: 02 Jun 2008.
Abstract
Recent evidence suggests an important role for hypothalamic orexins/hypocretins in
modulation of drug reward and addiction-like behaviors in rodents. Our recent study has
shown that the aversive state of arousal during acute morphine withdrawal is associated with
increased orexin gene expression in lateral hypothalamus (LH) of Fischer 344 (F344) inbred
rats, with no change in the expression of preprodynorphin (ppDyn), a gene co-expressed with
LH orexin. Therefore, we determined whether orexin and ppDyn mRNA levels in LH or medial
hypothalamus (including perifornical and dorsomedial areas) of F344 or Sprague-Dawley
(SD) outbred rats, are altered following: 1) cocaine (10 mg/kg, i.p.) conditioned place
preference (CPP); 2) chronic (14 days) cocaine exposure using both "binge" pattern
administration in steady-dose (45 mg/kg/day) and escalating-dose (45-90 mg/kg/day)
regimens; and 3) acute (1 day) and chronic (14 days) withdrawal from cocaine with opioid
receptor antagonist naloxone treatment (1 mg/kg). We found that orexin mRNA levels were
decreased after cocaine place conditioning in the LH of SD rats. A decreased LH orexin
mRNA level was also observed after chronic escalating-dose cocaine (but not CPP pattern
regimen without conditioning, or steady-dose regimen) in both strains. In F344 rats only,
acute withdrawal from chronic escalating-dose cocaine administration resulted in increases in
both LH orexin and ppDyn mRNA levels, which were unaltered by naloxone or after chronic
withdrawal. Our results suggest that (1) alteration of LH orexin gene expression is regionspecific after cocaine place conditioning in SD rats and dose-dependent after chronic
exposure in both strains; and (2) increased LH orexin and ppDyn gene expressions in F344
rats may contribute to negative affective states in cocaine withdrawal. copyright 2008 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 153
Issue Part 4
Page 1225-1234
Year of Publication 2008
Date of Publication 02 Jun 2008
COCAINE 2008 <494>
Database EMBASE
Accession Number 2008280653
Authors Minozzi S. Amato L. Davoli M. Farrell M. Lima Reisser A.A.R.L. Pani P.P. Silva De Lima M. Soares B.
Vecchi S.
Institution
(Minozzi) Department of Epidemiology, ASL RM E, via Pellicone 5, Fosdinovo 54035, Italy.
Country of Publication
United Kingdom
Title
Anticonvulsants for cocaine dependence.
Source
Cochrane Database of Systematic Reviews. (2), 2008. Article Number: CD006754. Date of
Publication: 2008.
Abstract
Background: Cocaine dependence is a major public health problem that is characterized by
recidivism and a host of medical and psychosocial complications. Although effective
pharmacotherapy is available for alcohol and heroin dependence none exists currently for
cocaine dependence despite two decades of clinical trials primarily involving antidepressant,
anti convulsivant and dopaminergic medications. There has been extensive consideration of
optimal pharmacological approaches to the treatment of cocaine dependence with
consideration of both dopamine antagonists and agonists. Anticonvulsants have been
candidates for the treatment of addiction based on the hypothesis that seizure kindling-like
mechanisms contribute to addiction. Objectives: To evaluate the efficacy and the acceptability
of anticonvulsants for cocaine dependence Search strategy: We searched the Cochrane
Drugs and Alcohol Groups specialised register (issue 4, 2007), MEDLINE (1966 - march
2007), EMBASE (1988 - march 2007), CINAHL (1982- to march 2007) Selection criteria: All
randomised controlled trials and controlled clinical trials which focus on the use of
anticonvulsants medication for cocaine dependence Data collection and analysis: Two
authors independently evaluated the papers, extracted data, rated methodological quality
Main results: Fifteen studies (1066 participants) met the inclusion criteria for this review: the
anticonvulsants drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin,
tiagabine, topiramate, valproate. No significant differences were found for any of the efficacy
measures comparing any anticonvulsants with placebo. Placebo was found to be superior to
gabapentin in diminishing the number of dropouts, two studies, 81 participants, Relative Risk
(RR) 3.56 (95% CI 1.07 to 11.82) and superior to phenythoin for side effects, two studies, 56
participants RR 2.12 (95% CI 1.08 to 4.17). All the other single comparisons are not
statistically significant. Authors' conclusions: Although caution is needed when assessing
results from a limited number of small clinical trials at present there is no current evidence
supporting the clinical use of anticonvulsants medications in the treatment of cocaine
dependence. Aiming to answer the urgent demand of clinicians, patients, families, and the
community as a whole for an adequate treatment for cocaine dependence, we need to
improve the primary research in the field of addictions in order to make the best possible use
out of a single study and to investigate the efficacy of other pharmacological agent. Copyright
copyright 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ISSN 1469-493X
Publication Type Journal: Review
Journal Name Cochrane Database of Systematic Reviews
Issue Part 2
Year of Publication 2008
Date of Publication 2008
COCAINE 2008 <507>
Database EMBASE
Accession Number 2008233561
Authors Thomas M.J. Kalivas P.W. Shaham Y.
Institution
(Thomas) Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States.
(Thomas) Department of Psychology, University of Minnesota, Minneapolis, MN, United States.
(Kalivas) Department of Neurosciences, Medical University of South Carolina, Charleston, SC, United States.
(Shaham) Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS, Baltimore, MD, United States.
(Thomas) Departments of Neuroscience and Psychology, University of Minnesota, 6-145 Jackson Hall, 321 Church
St. SE, Minneapolis, MN 55455, United States.
Country of Publication
United Kingdom
Title
Neuroplasticity in the mesolimbic dopamine system and cocaine addiction.
Source
British Journal of Pharmacology. 154(2)(pp 327-342), 2008. Date of Publication: May 2008.
Abstract
The main characteristics of cocaine addiction are compulsive drug use despite adverse
consequences and high rates of relapse during periods of abstinence. A current popular
hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced
neuroadaptations in reward-related learning and memory processes, which cause
hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habitlike learned behaviours that are insensitive to adverse consequences. Here, we review results
from studies on the effect of cocaine exposure on selected signalling cascades, growth
factors and physiological processes previously implicated in neuroplasticity underlying normal
learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling
pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic
plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We
also discuss the degree to which these cocaine-induced neuroplasticity changes in the
mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaineseeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on
how these factors may interact to initiate and sustain cocaine psychomotor sensitization and
cocaine seeking. copyright 2008 Nature Publishing Group All rights reserved.
ISSN 0007-1188
Publication Type Journal: Review
Journal Name British Journal of Pharmacology
Volume 154
Issue Part 2
Page 327-342
Year of Publication 2008
Date of Publication May 2008
COCAINE 2008 <555>
Database EMBASE
Accession Number 2008210806
Authors Hidalgo Carmona C.G. Santis Barros R. Rodriguez Tobar J. Hayden Canobra V. Anselmo Montequin E.
Institution
(Hidalgo Carmona) School of Psychology, Pontificia Universidad Catolica de Chile, Av. V.Mackenna 4860, Santiago
de Chile, Chile.
(Santis Barros, Hayden Canobra, Anselmo Montequin) School of Medicine, Pontificia Universidad Catolica de Chile,
Av. V.Mackenna 4860, Santiago de Chile, Chile.
(Rodriguez Tobar) School of Public Health, Universidad de Chile, Independencia 1027, Santiago de Chile, Chile.
Country of Publication
United Kingdom
Title
Family functioning of out-of-treatment cocaine base paste and cocaine hydrochloride
users.
Source
Addictive Behaviors. 33(7)(pp 866-879), 2008. Date of Publication: Jul 2008.
Abstract
Knowledge of family structure and behavioral dynamics of out-of-treatment drug users under
poverty becomes relevant, because of the role that the family plays in drug use and
rehabilitation. Hypotheses: 1. The perception of drug users about their family functioning
reveals a dysfunctional organization and communication-connection problems with their
families; and 2. the family system of cocaine base paste (CBP) users presents greater
dysfunctionality than cocaine hydrochloride (CH) users. Method: Cross-sectional descriptive
design of primary users of CH (n = 236) and primary users of CBP (n = 231) during the last
month, out-of-substance abuse treatment during the last 6 months. Instruments: Risk
Behavior Questionnaire and How-Is-Your-Family Questionnaire. Results: The total sample
presented 72.9% of families with risk functioning; CBP users registered a more deteriorated
family structure and communication-connection than CH users. Conclusions: CBP and CH
users, who are hidden from health treatment services, do indeed present a high degree of
family dysfunction; and the CBP group, compared to the CH group, presented various
indicators of greater risk in their family dysfunction. copyright 2008 Elsevier Ltd. All rights
reserved.
ISSN 0306-4603
Publication Type Journal: Article
Journal Name Addictive Behaviors
Volume 33
Issue Part 7
Page 866-879
Year of Publication 2008
Date of Publication Jul 2008
COCAINE 2008 <561>
Database EMBASE
Accession Number 2008202002
Authors Bachtell R.K. Choi K.-H. Simmons D.L. Falcon E. Monteggia L.M. Neve R.L. Self D.W.
Institution
(Bachtell, Choi, Simmons, Falcon, Monteggia, Self) Department of Psychiatry, University of Texas, Southwestern
Medical Center, Dallas, TX 75390, United States.
(Neve) Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, United States.
Country of Publication
United Kingdom
Title
Role of GluR1 expression in nucleus accumbens neurons in cocaine sensitization and
cocaine-seeking behavior.
Source
European Journal of Neuroscience. 27(9)(pp 2229-2240), 2008. Date of Publication: May
2008.
Abstract
Chronic cocaine use reduces glutamate levels in the nucleus accumbens (NAc), and is
associated with experience-dependent changes in (+/-)-alpha-amino-3-hydroxy-5methylisoxazole-4-propionic acid (AMPA) glutamate receptor membrane expression in NAc
neurons. These changes accompany behavioral sensitization to cocaine and increased
susceptibility to cocaine relapse. The functional relationship between neuroplasticity in AMPA
receptors and the behavioral manifestation of cocaine addiction remains unclear. Thus, we
examined the behavioral effects of up- and downregulating basal AMPA receptor function in
the NAc core and shell using viral-mediated gene transfer of wild-type glutamate receptor 1
(wt-GluR1) or a dominant-negative pore-dead GluR1 (pd-GluR1), respectively. Transient
increases in wt-GluR1 during or after cocaine treatments diminished the development of
cocaine sensitization, while pd-GluR1 expression exacerbated cocaine sensitization. Parallel
changes were found in D2, but not D1, receptor-mediated behavioral responses. As a
correlate of the sensitization experiments, we overexpressed wt- or pd-GluR1 in the NAc core
during cocaine self-administration, and tested the effects on subsequent drug-seeking
behavior 3 weeks after overexpression declined. wt-GluR1 overexpression during selfadministration had no effect on cocaine intake, but subsequently reduced cocaine seeking in
extinction and cocaine-induced reinstatement, whereas pd-GluR1 facilitated cocaine-induced
reinstatement. When overexpressed during reinstatement tests, wt-GluR1 directly attenuated
cocaine- and D2 agonist-induced reinstatement, while pd-GluR1 enhanced reinstatement. In
both experimental procedures, neither wt- nor pd-GluR1 expression affected cue-induced
reinstatement. Together, these results suggest that degrading basal AMPA receptor function
in NAc neurons is sufficient to facilitate relapse via sensitization in D2 receptor responses,
whereas elevating basal AMPA receptor function attenuates these behaviors. copyright The
Authors (2008).
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 27
Issue Part 9
Page 2229-2240
Year of Publication 2008
Date of Publication May 2008
COCAINE (A) 2008 <571>
Database EMBASE
Accession Number 2008192078
Authors Kelai S. Maussion G. Noble F. Boni C. Ramoz N. Moalic J.-M. Peuchmaur M. Gorwood P. Simonneau M.
Institution
(Kelai, Maussion, Boni, Ramoz, Moalic, Gorwood, Simonneau) INSERM U675, School of Medicine Xavier Bichat,
University Denis Diderot, Paris VII, Paris, France.
(Noble) University Paris Descartes, CNRS UMR 7157, INSERM U705, Paris, France.
(Peuchmaur) Department of Pathology, EA-3102, Robert Debre Hospital, Paris, France.
(Simonneau) INSERM U675, IFR02, Faculte de Medecine Xavier Bichat, 16 Rue Henri Huchard, 75018 Paris,
France.
Country of Publication
United Kingdom
Title
Nrxn3 upregulation in the globus pallidus of mice developing cocaine addiction.
Source
NeuroReport. 19(7)(pp 751-755), 2008. Date of Publication: May 2008.
Abstract
Dysfunctions affecting the connections of basal ganglia lead to major neurological and
psychiatric disorders. We investigated levels of mRNA for three neurexins (Nrxn) and three
neuroligins (Nlgn) in the globus pallidus, subthalamic nucleus, and substantia nigra, in control
conditions and after short-term exposure to cocaine. The expression of Nrxn2beta and Nlgn3
in the substantia nigra and Nlgn1 in the subthalamic nucleus depended on genetic
background. The development of short-term cocaine appetence induced an increase in
Nrxn3beta expression in the globus pallidus. Human NRXN3 has recently been linked to
several addictions. Thus, NRXN3 adhesion molecules may play an important role in the
synaptic plasticity of neurons involved in the indirect pathways of basal ganglia, in which they
regulate reward-related learning. copyright 2008 Lippincott Williams & Wilkins, Inc.
ISSN 0959-4965
Publication Type Journal: Article
Journal Name NeuroReport
Volume 19
Issue Part 7
Page 751-755
Year of Publication 2008
Date of Publication May 2008
COCAINE 2008 <580>
Database EMBASE
Accession Number 2008160185
Authors Paletzki R.F. Myakishev M.V. Polesskaya O. Orosz A. Hyman S.E. Vinson C.
Institution
(Paletzki, Hyman) Laboratory of Molecular Pathophysiology, National Institute of Neurological Disorders and Stroke,
NIH, Building 36, Room 4C-24, Bethesda, MD 20892, United States.
(Myakishev, Orosz, Vinson) Laboratory of Metabolism, National Cancer Institute, NIH, Building 37, Room 3128,
Bethesda, MD 20892, United States.
(Polesskaya) Department of Psychology, George Mason University, Discovery Hall PW2, 10900 University
Boulevard, Manassas, VA 20110, United States.
Country of Publication
United Kingdom
Title
Inhibiting activator protein-1 activity alters cocaine-induced gene expression and
potentiates sensitization.
Source
Neuroscience. 152(4)(pp 1040-1053), 2008. Date of Publication: 09 Apr 2008.
Abstract
We have expressed A-FOS, an inhibitor of activator protein-1 (AP-1) DNA binding, in adult
mouse striatal neurons. We observed normal behavior including locomotion and exploratory
activities. Following a single injection of cocaine, locomotion increased similarly in both the AFOS expressing and littermate controls. However, following repeated injections of cocaine,
the A-FOS expressing mice showed increased locomotion relative to littermate controls, an
increase that persisted following a week of withdrawal and subsequent cocaine
administration. These results indicate that AP-1 suppresses this behavioral response to
cocaine. We analyzed mRNA from the striatum before and 4 and 24 h after a single cocaine
injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to
identify genes mis-regulated by A-FOS that may mediate the increased locomotor
sensitization to cocaine. A-FOS expression did not change gene expression in the basal state
or 4 h following cocaine treatment relative to controls. However, 24 h after an acute cocaine
treatment, 84 genes were identified that were differentially expressed between the A-FOS and
control mice. Fifty-six genes are down-regulated while 28 genes are up-regulated including
previously identified candidates for addiction including brain-derived neurotrophic factor and
period homolog 1. Using a random sample of identified genes, quantitative PCR was used to
verify the microarray studies. The chromosomal location of these 84 genes was compared
with human genome scans of addiction to identify potential genes in humans that are involved
in addiction. copyright 2008 IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 152
Issue Part 4
Page 1040-1053
Year of Publication 2008
Date of Publication 09 Apr 2008
COCAINE 2008 <611>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 18173840
Status In-Data-Review
Authors Guindalini C. Laranjeira R. Collier D. Messas G. Vallada H. Breen G.
Authors Full Name Guindalini, Camila. Laranjeira, Ronaldo. Collier, David. Messas, Guilherme. Vallada, Homero.
Breen, Gerome.
Institution
MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College
London, UK. [email protected]
Title
Dopamine-beta hydroxylase polymorphism and cocaine addiction.
Source
Behavioral & Brain Functions [Electronic Resource]: BBF. 4:1, 2008.
Journal Name
Behavioral & Brain Functions [Electronic Resource]: BBF
Other ID
Source: NLM. PMC2263049
Country of Publication
England
Abstract
ABSTRACT: Cocaine addiction involves a number of medical, psychological and social
problems. Understanding the genetic aetiology of this disorder will be essential for design of
effective treatments. Dopamine-beta hydroxylase (DbH) catalyzes the conversion of
dopamine to norepinephrine and could, therefore, have an influence on both cocaine action
and the basal sensitivity of neurotransmitter systems to cocaine. Recently, the -1021C>T
polymorphism have been found to strongly correlated with individual variation in plasma DbH
activity. To test the influence of this polymorphism on the susceptibility of cocaine addiction,
we decided to genotype it in a sample of 689 cocaine addicts and 832 healthy individuals.
Genotypic and allelic analyses did not show any evidence of association with cocaine
addiction, even after correcting for the effect of population stratification and other possible
confounders. Our results do not support a major role of the -1021C>T polymorphism or the
gene itself in the development of cocaine addiction but further examination of other variants
within this gene will be necessary to completely rule out an effect.
Publication Type Journal Article.
Date of Publication 2008
Year of Publication 2008
Volume 4
Page 1
COCAINE 2008 <609>
Database EMBASE
Accession Number 2008164704
Authors Karila L. Gorelick D. Weinstein A. Noble F. Benyamina A. Coscas S. Blecha L. Lowenstein W. Martinot J.L.
Reynaud M. Lepine J.P.
Institution
(Karila) INSERM, U797, Research Unit 'Neuroimaging and Psychiatry', Hospital Department Frederic Joliot, Orsay,
France.
(Karila) Univ. Paris-Sud, Univ. Paris V Rene Descartes,
(Karila, Benyamina, Coscas, Blecha, Reynaud) AP-HP, Hopital Universitaire Paul Brousse, Centre d'Enseignement,
de Recherche et de Traitement des Addictions, Villejuif F-94808, France.
(Gorelick) Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore,
MD, United States.
(Weinstein) Department of Medical Biophysics and Nuclear Medicine, Hadassah Hospital Ein Kerem, Jerusalem,
Israel.
(Noble) Universite Paris Descartes, Faculte de Pharmacie, Neuropsychopharmacologie des Addictions, UMR7157,
France.
(Benyamina, Coscas, Blecha, Reynaud) Universite Paris-Sud, INSERM U669, Paris, F-75014, France.
(Lowenstein) Montevideo Clinic, Boulogne-Billancourt, France.
(Martinot) INSERM, U797, 'Neuroimaging and Psychiatry' Unit, Hospital Department Frederic Joliot, Orsay, France.
(Martinot) Univ. Paris-Sud, Univ. Paris V Rene Descartes, France.
(Lepine) Universite Paris Descartes, Faculte de Pharmacie, Neuropsychopharmacologie des Addictions, Service de
Psychiatrie, Paris F-75010, France.
(Karila) Hopital Paul Brousse, CERTA (Centre d'Enseignement, de Recherche, de Traitement des Addictions), 12
Avenue Paul Vaillant-Couturier, Villejuif 94800, France.
Country of Publication
United Kingdom
Title
New treatments for cocaine dependence: A focused review.
Source
International Journal of Neuropsychopharmacology. 11(3)(pp 425-438), 2008. Date of
Publication: May 2008.
Abstract
Cocaine, already a significant drug problem in North and South America, has become a
more prominent part of the European drug scene. Cocaine dependence has major somatic,
psychological, psychiatric, socio-economic, and legal implications. No specific effective
pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology
have identified various neuronal mechanisms implicated in cocaine addiction and suggested
several promising pharmacological approaches. Data were obtained from Medline, EMBASE,
and PsycINFO searches of English-language articles published between 1985 and June 2007
using the key words: cocaine, addiction, cocaine dependence, clinical trials,
pharmacotherapy(ies) singly and in combination. Large well-controlled studies with
appropriate statistical methods were preferred. Pharmacological agents such as GABA
agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents
(modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of
cocaine dependence. The results from trials of first- and second-generation neuroleptics are
largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the
serotonergic system, shows some promise. Preliminary results of human studies with anticocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several
compounds in preclinical development. While no medication has received regulatory approval
for the treatment of cocaine dependence, several medications marketed for other indications
have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in
preclinical development have also shown promise. Findings from early clinical trials must be
confirmed in larger, less selective patient populations. copyright 2008 Collegium
Internationale Neuropsychopharmacologicum.
ISSN 1461-1457
Publication Type Journal: Review
Journal Name International Journal of Neuropsychopharmacology
Volume 11
Issue Part 3
Page 425-438
Year of Publication 2008
Date of Publication May 2008
COCAINE 2008 <742>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 18640911
Status MEDLINE
Authors Garavan H. Kaufman JN. Hester R.
Authors Full Name Garavan, Hugh. Kaufman, Jacqueline N. Hester, Robert.
Institution
Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin 2, Ireland. [email protected]
Title
Acute effects of cocaine on the neurobiology of cognitive control.
Source
Philosophical Transactions of the Royal Society of London - Series B: Biological Sciences.
363(1507):3267-76, 2008 Oct 12.
Journal Name
Philosophical Transactions of the Royal Society of London - Series B: Biological Sciences
Other ID
Source: NLM. PMC2607334
Country of Publication
England
Abstract
Compromised ability to exert control over drug urges and drug-seeking behaviour is a
characteristic of addiction. One specific cognitive control function, impulse control, has been
shown to be a risk factor for the development of substance problems and has been linked in
animal models to increased drug administration and relapse. We present evidence of a direct
effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor
response inhibition, an intravenous cocaine administration improved task performance in 13
cocaine users. This improvement was accompanied by increased activation in right
dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function.
Similarly, for both inhibitory control and action monitoring processes, cocaine normalized
activation levels in lateral and medial prefrontal regions previously reported to be hypoactive
in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction
may reflect a chronic dysregulation of those brain regions and the cognitive processes they
subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically
mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive
control.
Publication Type Comparative Study. Journal Article. Research Support, N.I.H., Extramural.
Date of Publication 2008 Oct 12
Year of Publication 2008
Issue/Part 1507
Volume 363
Page 3267-76
COCAINE (A) 2008<745>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 18751519
Status MEDLINE
Authors Bradberry CW.
Authors Full Name Bradberry, Charles W.
Institution
Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, PA15203, USA.
[email protected]
Title
Comparison of acute and chronic neurochemical effects of cocaine and cocaine cues in
rhesus monkeys and rodents: focus on striatal and cortical dopamine systems. [Review] [99
refs]
Source
Reviews in the Neurosciences. 19(2-3):113-28, 2008.
Journal Name
Reviews in the Neurosciences
Country of Publication
England
Abstract
Preclinical work into the effects of cocaine on mesostriatal and mesocorticolimbic dopamine
systems has rightly been dominated by studies in rodent models. From the wealth of data that
has resulted from those studies, models of chronic neurobiological adaptations have been
developed that might illuminate the cellular and systems bases for the compulsive and selfinjurious aspects of addiction. Chronic adaptations of dopaminergic mechanisms often
dominate these models. Our studies into the acute and chronic dopaminergic effects of
cocaine in non-human primates are compared to important aspects of the larger rodent
literature. In some ways there is good concordance, but in others the non-human primate
results differ in ways that are more similar to the human literature. This is especially true in
regard to sensitization of dopamine systems in response to chronic self-administration. To
best evaluate potential models of addiction, it will be important to also consider data from nonhuman primates as a more proximal animal model to the human condition, particularly in the
greater complexity of cortical development. [References: 99]
ISSN Print 0334-1763
Publication Type Journal Article. Research Support, N.I.H., Extramural. Research Support, U.S. Gov't, NonP.H.S.. Review.
Date of Publication 2008
Year of Publication 2008
Issue/Part 2-3
Volume 19
Page113-28
COCAINE 2008 <770>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 18425968
Status MEDLINE
Authors Minozzi S. Amato L. Davoli M. Farrell M. Lima Reisser AA. Pani PP. Silva de Lima M. Soares B. Vecchi
S.
Authors Full Name Minozzi, S. Amato, L. Davoli, M. Farrell, M. Lima Reisser, A A R L. Pani, P P. Silva de Lima,
M. Soares, B. Vecchi, S.
Institution
ASL RM E, Department of Epidemiology, via Pellicone 5, Fosdinovo, Italy, 54035. [email protected]
Title
Anticonvulsants for cocaine dependence. [Review] [92 refs]
Source
Cochrane Database of Systematic Reviews. (2):CD006754, 2008.
Journal Name
Cochrane Database of Systematic Reviews
Country of Publication
England
Abstract
BACKGROUND: Cocaine dependence is a major public health problem that is characterized
by recidivism and a host of medical and psychosocial complications. Although effective
pharmacotherapy is available for alcohol and heroin dependence none exists currently for
cocaine dependence despite two decades of clinical trials primarily involving antidepressant,
anti convulsivant and dopaminergic medications. There has been extensive consideration of
optimal pharmacological approaches to the treatment of cocaine dependence with
consideration of both dopamine antagonists and agonists. Anticonvulsants have been
candidates for the treatment of addiction based on the hypothesis that seizure kindling-like
mechanisms contribute to addiction. OBJECTIVES: To evaluate the efficacy and the
acceptability of anticonvulsants for cocaine dependence SEARCH STRATEGY: We searched
the Cochrane Drugs and Alcohol Groups specialised register (issue 4, 2007), MEDLINE
(1966 - march 2007), EMBASE (1988 - march 2007), CINAHL (1982- to march 2007)
SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials which
focus on the use of anticonvulsants medication for cocaine dependence DATA COLLECTION
AND ANALYSIS: Two authors independently evaluated the papers, extracted data, rated
methodological quality MAIN RESULTS: Fifteen studies (1066 participants) met the inclusion
criteria for this review: the anticonvulsants drugs studied were carbamazepine, gabapentin,
lamotrigine, phenytoin, tiagabine, topiramate, valproate. No significant differences were found
for any of the efficacy measures comparing any anticonvulsants with placebo. Placebo was
found to be superior to gabapentin in diminishing the number of dropouts, two studies, 81
participants, Relative Risk (RR) 3.56 (95% CI 1.07 to 11.82) and superior to phenythoin for
side effects, two studies, 56 participants RR 2.12 (95% CI 1.08 to 4.17). All the other single
comparisons are not statistically significant. AUTHORS' CONCLUSIONS: Although caution is
needed when assessing results from a limited number of small clinical trials at present there
is no current evidence supporting the clinical use of anticonvulsants medications in the
treatment of cocaine dependence. Aiming to answer the urgent demand of clinicians, patients,
families, and the community as a whole for an adequate treatment for cocaine dependence,
we need to improve the primary research in the field of addictions in order to make the best
possible use out of a single study and to investigate the efficacy of other pharmacological
agent. [References: 92]
Publication Type Journal Article. Meta-Analysis. Review.
Date of Publication 2008
Year of Publication 2008
Issue/Part 2
Page CD006754
AMPHETAMINES / COCAINE 2008 <764>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 17535480
Status MEDLINE
Authors Amigo S. Caselles A. Mico JC.
Authors Full Name Amigo, Salvador. Caselles, Antonio. Mico, Joan C.
Institution
Departament de Personalitat, Avaluacio i Tractaments Psicologics, Universitat de Valencia, Spain.
Title
A dynamic extraversion model. The brain's response to a single dose of a stimulant
drug.
Source
British Journal of Mathematical & Statistical Psychology. 61(Pt 1):211-31, 2008 May.
Journal Name
British Journal of Mathematical & Statistical Psychology
Country of Publication
England
Abstract
The aim of this paper is to present a mathematical dynamic modelling of the effect a
stimulant drug has on different people which, at the same time, can be a useful tool for future
brain studies. To this end, a dynamic model of the evolution of extraversion (considering its
tonic and phasic aspects) has been constructed taking into account the unique personality
trait theory and the general modelling methodology. This model consists of a delayed
differential equation which, on one hand, considers that the active stimulus, a consequence of
a single intake, is not constant; on the other hand, it contemplates that the state variable
representing the phasic extraversion also represents the brain activation. The derivative of
this state variable is calculated as the sum of the homeostatic control flow, the excitatory
effect flow and the inhibitor effect flow. The solutions of this equation relate the tonic
activation of an individual (that characterizes his or her personality) with his or her phasic
activation level, whose evolution over time describes the organism's response to a single drug
intake. These solutions quantitatively reproduce the predictions of current personality theories
and anticipate vulnerability to drug misuse and addiction development.
ISSN Print 0007-1102
Publication Type Journal Article.
Date of Publication 2008 May
Year of Publication 2008
Issue/Part Pt 1
Volume 61
Page 211-31
COCAINE 2008 <779>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 18292872
Status MEDLINE
Authors Zheng F. Zhan CG.
Authors Full Name Zheng, Fang. Zhan, Chang-Guo.
Institution
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington,
KY 40536, USA.
Title
Structure-and-mechanism-based design and discovery of therapeutics for cocaine
overdose and addiction. [Review] [55 refs]
Source
Organic & Biomolecular Chemistry. 6(5):836-43, 2008 Mar 7.
Journal Name
Organic & Biomolecular Chemistry
Country of Publication
England
Abstract
(-)-Cocaine is a widely abused drug and there is currently no available anti-cocaine
therapeutic. Promising agents, such as anti-cocaine catalytic antibodies and high-activity
mutants of human butyrylcholinesterase (BChE), for therapeutic treatment of cocaine
overdose have been developed through structure-and-mechanism-based design and
discovery. In particular, a unique computational design strategy based on the modeling and
simulation of the rate-determining transition state has been developed and used to design
and discover desirable high-activity mutants of BChE. One of the discovered high-activity
mutants of BChE has a approximately 456-fold improved catalytic efficiency against (-)cocaine. The encouraging outcome of the structure-and-mechanism-based design and
discovery effort demonstrates that the unique computational design approach based on
transition state modeling and simulation is promising for rational enzyme redesign and drug
discovery. The general approach of the structure-and-mechanism-based design and
discovery may be used to design high-activity mutants of any enzyme or catalytic antibody.
[References: 55]
ISSN Print 1477-0520
Publication Type Journal Article. Research Support, N.I.H., Extramural. Review.
Date of Publication
2008 Mar 7
Year of Publication 2008
Issue/Part 5
Volume 6
Page 836-43
COCAINE (A) 2008 <789>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 17559417
Status MEDLINE
Authors Hodge CW. Bratt AM. Kelley SP.
Authors Full Name Hodge, C W. Bratt, A M. Kelley, S P.
Institution
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
[email protected]
Title
Deletion of the 5-HT(3A)-receptor subunit blunts the induction of cocaine
sensitization.
Source
Genes, Brain, & Behavior. 7(1):96-102, 2008 Feb.
Journal Name
Genes, Brain, & Behavior
Other ID
Source: NLM. NIHMS51109
Source: NLM. PMC2533739
Country of Publication
England
Abstract
Serotonin (5-HT) receptors are classified into seven groups (5-HT(1-7)), comprising at least
14 structurally and pharmacologically distinct receptor subtypes. Pharmacological antagonism
of ionotropic 5-HT(3) receptors has been shown to modulate both behavioral and
neurochemical aspects of the induction of sensitization to cocaine. It is not known, however, if
specific molecular subunits of the 5-HT(3) receptor influence the development of cocaine
sensitization. To address this question, we studied the effects of acute and chronic
intermittent cocaine administration in mice with a targeted deletion of the gene for the 5HT(3A)-receptor subunit (5-HT(3A)-/-). 5-HT(3A) (-/-) mice showed blunted induction of
cocaine-induced locomotor sensitization as compared with wild-type littermate controls. 5HT(3A) (-/-) mice did not differ from wild-type littermate controls on measures of basal motor
activity or response to acute cocaine treatment. Enhanced locomotor response to saline
injection following cocaine sensitization was observed equally in 5-HT(3A) (-/-) and wild-type
mice suggesting similar conditioned effects associated with chronic cocaine treatment. These
data show a role for the 5-HT(3A)-receptor subunit in the induction of behavioral sensitization
to cocaine and suggest that the 5-HT(3A) molecular subunit modulates neurobehavioral
adaptations to cocaine, which may underlie aspects of addiction.
Publication Type Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't.
Date of Publication 2008 Feb
Year of Publication 2008
Issue/Part 1
Volume 7
Page 96-102
COCAINE (A) 2008 <790>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 17897630
Status MEDLINE
Authors Rothman RB. Baumann MH. Prisinzano TE. Newman AH.
Authors Full Name Rothman, Richard B. Baumann, Michael H. Prisinzano, Thomas E. Newman, Amy Hauck.
Institution
Clinical Psychopharmacology Section, National Institute on Drug Abuse, Intramural Research Program, National
Institutes of Health, 333 Cassell Dr., Baltimore, MD 21224, USA.
Title
Dopamine transport inhibitors based on GBR12909 and benztropine as potential
medications to treat cocaine addiction. [Review] [95 refs]
Source
Biochemical Pharmacology. 75(1):2-16, 2008 Jan 1.
Journal Name
Biochemical Pharmacology
Other ID
Source: NLM. NIHMS37107
Source: NLM. PMC2225585
Country of Publication
England
Abstract
The discovery and development of medications to treat addiction and notably, cocaine
addiction, have been frustrated by both the complexity of the disorder and the lack of target
validation in human subjects. The dopamine transporter has historically been a primary target
for cocaine abuse medication development, but addictive liability and other confounds of such
inhibitors of dopamine uptake have limited clinical evaluation and validation. Herein we
describe efforts to develop analogues of the dopamine uptake inhibitors GBR 12909 and
benztropine that show promising profiles in animal models of cocaine abuse that contrast to
that of cocaine. Their unique pharmacological profiles have provided important insights into
the reinforcing actions of cocaine and we propose that clinical investigation of novel dopamine
uptake inhibitors will facilitate the discovery of cocaine-abuse medications. [References: 95]
ISSN Print 0006-2952
Publication Type Journal Article. Research Support, N.I.H., Intramural. Review.
Date of Publication 2008 Jan 1
Year of Publication 2008
Issue/Part 1
Volume 75
Page 2-16