COCAINE (A) 2006 <889>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 17050842
Status MEDLINE
Authors Carter K. Lukowiak K. Schenk JO. Sorg BA.
Authors Full Name Carter, Kathleen. Lukowiak, Ken. Schenk, James O. Sorg, Barbara A.
Institution
Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology,
Washington State University, Pullman, WA 99164, USA.
Title
Repeated cocaine effects on learning, memory and extinction in the pond snail
Lymnaea stagnalis.
Source
Journal of Experimental Biology. 209(Pt 21):4273-82, 2006 Nov.
Journal Name
Journal of Experimental Biology
Country of Publication
England
Abstract
The persistence of drug addiction suggests that drugs of abuse enhance learning and/or
impair extinction of the drug memory. We studied the effects of repeated cocaine on learning,
memory and reinstatement in the pond snail, Lymnaea stagnalis. Respiratory behavior can be
operantly conditioned and extinguished in Lymnaea, and this behavior is dependent on a
critical dopamine neuron. We tested the hypothesis that repeated cocaine exposure promotes
learning and memory or attenuates the ability to extinguish the memory of respiratory
behavior that relies on this dopaminergic neuron. Rotating disk electrode voltammetry
revealed a K(m) and V(max) of dopamine uptake in snail brain of 0.9 micromol l(-1) and 558
pmol s(-1) g(-1) respectively, and the IC(50) of cocaine for dopamine was approximately 0.03
micromol l(-1). For operant conditioning, snails were given 5 days of 1 h day(-1) immersion in
water (control) or 0.1 micromol l(-1) cocaine, which was the lowest dose that maximally
inhibited dopamine uptake, and snails were trained 3 days later. No changes were found
between the two groups for learning or memory of the operant behavior. However, snails
treated with 0.1 micromol l(-1) cocaine demonstrated impairment of extinction memory during
reinstatement of the behavior compared with controls. Our findings suggest that repeated
exposure to cocaine modifies the interaction between the original memory trace and active
inhibition of this trace through extinction training. An understanding of these basic processes
in a simple model system may have important implications for treatment strategies in cocaine
addiction.
ISSN Print 0022-0949
Publication Type Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't.
Date of Publication 2006 Nov
Year of Publication 2006
Issue/Part Pt 21
Volume 209
Page 4273-82
COCAINE / OPIOIDS 2006 <401>
Database EMBASE
Accession Number 2007221706
Authors Aouizerate B. Ho A. Schluger J.H. Perret G. Borg L. Le Moal M. Piazza P.V. Kreek M.J.
Institution
(Aouizerate, Le Moal, Piazza) Laboratory of Pathophysiology of Behavior, Victor Segalen's University (Bordeaux 2),
France.
(Ho, Schluger, Perret, Borg, Kreek) Laboratory of the Biology of Addictive Diseases, Rockefeller University, United
States.
(Kreek) Laboratory of the Biology of Addictive Diseases, Rockefeller University, 1230 York Avenue, New York, NY
10021, United States.
Country of Publication
United Kingdom
Title
Glucocorticoid negative feedback in methadone-maintained former heroin addicts
with ongoing cocaine dependence: Dose-response to dexamethasone suppression.
Source
Addiction Biology. 11(1)(pp 84-96), 2006. Date of Publication: Mar 2006.
Abstract
Combined cocaine and illicit opiate use is common. This study aimed to test the hypothesis
that cocaine dependence in former heroin-addicted patients maintained on methadone
treatment is associated with enhanced glucocorticoid negative feedback. Multiple dose
dexamethasone suppression tests, using a conventional 2.0 mg dose, and two lower doses,
0.5 mg and 0.125 mg, were performed in 10 methadone-maintained former heroin addicts
with ongoing cocaine dependence (C-MM), 10 stabilized methadone-maintained former
heroin addicts with no ongoing drug or alcohol use (MM), and 22 normal volunteers (NV). At 9
hours, there was no difference in plasma adrenocorticotropin hormone (ACTH) and/or cortisol
levels among groups on the baseline day, as well as after the two lower doses of
dexamethasone. At 17 hours, C-MM and MM had significantly lower plasma ACTH and/or
cortisol levels than NV. However, C-MM did not significantly differ from MM in their hormonal
levels. When the hormonal responses to dexamethasone are expressed as magnitude of
lowering from baseline, there was no significant difference at any dose among groups.
Therefore, C-MM exhibited a normal glucocorticoid negative feedback in the morning. Using
the standard interpretation of dexamethasone suppression testing based on the examination
of the actual hormonal levels rather than the difference from baseline condition, C-MM appear
to have glucocorticoid effects similar to MM, yet were both greater than NV in the late
afternoon. Thus, further studies are needed to know whether altered glucocorticoid negative
feedback is related to chronic cocaine exposure, or is the result of former heroin addiction
and/or its long-term treatment with methadone. copyright 2006 The Authors.
ISSN 1355-6215
Publication Type Journal: Article
Journal Name Addiction Biology
Volume 11
Issue Part 1
Page 84-96
Year of Publication 2006
Date of Publication Mar 2006
COCAINE 2006 <425>
Database EMBASE
Accession Number 2007003795
Authors Ross M.W. Risser J. Peters Jr. R.J. Johnson R.J.
Institution
(Ross, Risser, Peters Jr., Johnson) WHO Center for Health Promotion and Prevention Research, School of Public
Health, University of Texas-Houston, Houston, TX, United States.
(Johnson) School of Nursing, University of Texas-Austin,
(Ross) WHO Center for Health Promotion and Prevention Research, School of Public Health, University of TexasHouston, PO Box 20036, Houston, TX 77225, United States.
Country of Publication
United Kingdom
Title
Cocaine use and syphilis trends: Findings from the arrestee drug abuse monitoring
(ADAM) program and syphilis epidemiology in Houston.
Source
American Journal on Addictions. 15(6)(pp 473-477), 2006. Date of Publication: Nov 2006.
Abstract
There has been speculation that trends in syphilis have been fueled by crack cocaine use.
This study examined the data on syphilis notifications and arrestee drug abuse monitoring
(ADAM) to ascertain the relationships between syphilis and cocaine use trends in three
racial/ethnic groups. Syphilis notifications and data from the ADAM project were compared in
Houston/Harris County, Texas, from 1991-1998 using a linear regression equation. Data
indicated significant relationships between the data for cocaine use and syphilis in African
Americans but not Hispanics or non-Hispanic whites. For African Americans, 58% of the
variance between cocaine use and syphilis was explained. When data limited to jail syphilis
notifications and ADAM cocaine in African Americans were examined, the association was
stronger for males than for females. For African Americans, cocaine (probably crack cocaine)
use trends were significantly associated with syphilis trends in this population. These data
suggest that control of crack cocaine may have an impact on syphilis rates and that there may
be close relationships between some STDs and drug abuse. Copyright copyright American
Academy of Addiction Psychiatry.
ISSN 1055-0496
Publication Type Journal: Article
Journal Name American Journal on Addictions
Volume 15
Issue Part 6
Page 473-477
Year of Publication 2006
Date of Publication Nov 2006
COCAINE 2006 <431>
Database EMBASE
Accession Number 2007003789
Authors Ahmadi J. Kampman K. Dackis C.
Institution
(Ahmadi, Kampman, Dackis) Treatment Research Center, Department of Psychiatry, University of Pennsylvania,
Philadelphia, PA, United States.
(Ahmadi) Department of Psychiatry, Shiraz University of Medical Sciences, Shiraz, Iran, Islamic Republic of.
(Ahmadi) Department of Psychiatry, University of Medical Sciences, PO Box 71345-1416, Shiraz, Iran, Islamic
Republic of.
Country of Publication
United Kingdom
Title
Outcome predictors in cocaine dependence treatment trials.
Source
American Journal on Addictions. 15(6)(pp 434-439), 2006. Date of Publication: Nov 2006.
Abstract
Finding the predictors of outcome in outpatient cocaine dependence treatment trials may be
useful for the development of both psychosocial as well as pharmacological treatments for
cocaine dependence. Among the most powerful predictors of response to psychosocial
treatment are cocaine withdrawal symptom severity and the results of a urine drug screen
(UDS) collected at study entry. The present trial seeks to extend these findings by examining
outcome predictors in a large number of subjects participating in a series of outpatient
cocaine pharmacotherapy trials while selecting three separate criteria to define successful
outcome. The ability of several baseline variables were tested to predict treatment outcome in
a series of cocaine medication trials that included 402 cocaine-dependent subjects. Predictor
variables included results from the baseline Addiction Severity Index (ASI), initial UDS results,
and cocaine withdrawal symptom severity at treatment entry, as measured by scores on the
Cocaine Selective Severity Assessment (CSSA). Outcome measures included UDS results
obtained during the trials and results from the ASI gathered at the end of the trials. Baseline
variables that most consistently predicted treatment outcome were the initial UDS results and
initial CSSA scores. These findings indicate that baseline UDS results and CSSA scores are
powerful predictors of outcome and should be used as stratifying variables in outpatient
cocaine medication trials. Copyright copyright American Academy of Addiction Psychiatry.
ISSN 1055-0496
Publication Type Journal: Article
Journal Name American Journal on Addictions
Volume 15
Issue Part 6
Page 434-439
Year of Publication 2006
Date of Publication Nov 2006
COCAINE (A) 2006 <436>
Database EMBASE
Accession Number 2006623337
Authors Di Pietro N.C. Black Y.D. Kantak K.M.
Institution
(Di Pietro, Black, Kantak) Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University,
Boston, MA 02215, United States.
Country of Publication
United Kingdom
Title
Context-dependent prefrontal cortex regulation of cocaine self-administration and
reinstatement behaviors in rats.
Source
European Journal of Neuroscience. 24(11)(pp 3285-3298), 2006. Date of Publication: Dec
2006.
Abstract
Evidence of stimulus attribute-specificity within the prefrontal cortex (PFC) suggests that
different prefrontal subregions may contribute to cocaine addiction in functionally distinct
ways. Thus, the present study examined the effects of lidocaine-induced inactivation of two
distinct PFC subregions, the prelimbic (PL) or dorsal agranular insular (AId) cortices, on drugseeking and drug-taking behaviors under cocaine maintenance and reinstatement testing
conditions in rats trained to self-administer 1 mg/kg cocaine under a second-order schedule of
drug delivery. Throughout maintenance and reinstatement phases, rats were exposed to
conditioned light cues and contextual odor or sound cues. Results showed that PL
inactivation during maintenance test sessions significantly reduced drug-seeking and drugtaking behaviors, and disrupted patterns of responding in rats exposed to light-sound, but not
light-odor, cues. Moreover, lidocaine-induced inactivation of the PL significantly attenuated
drug-seeking behavior during cue-induced and cocaine prime-induced reinstatement in rats
exposed to light-sound cues only. In contrast, AId inactivation significantly attenuated cueinduced reinstatement of drug-seeking behavior in rats exposed to light-odor cues only. Drugseeking and drug-taking behaviors in these rats were not disrupted during maintenance and
cocaine prime-induced reinstatement testing regardless of the type of contextual cues used.
Together, these data suggest that PL and AId subregions play separate yet overlapping roles
in regulating cocaine addiction in rats in ways that are dependent on the presence or absence
of cocaine and on the types of contextual cues present in the cocaine self-administration
environment. copyright The Authors (2006).
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 24
Issue Part 11
Page 3285-3298
Year of Publication 2006
Date of Publication Dec 2006
COCAINE 2006 <464>
Database EMBASE
Accession Number 2006576076
Authors Lu L. Koya E. Zhai H. Hope B.T. Shaham Y.
Institution
(Lu, Zhai) Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing,
100083, China.
(Koya, Hope, Shaham) Behavioral Neuroscience Branch, IRP, NIDA, 5500 Nathan Shock Drive, Baltimore, MD
21224, United States.
Country of Publication
United Kingdom
Title
Role of ERK in cocaine addiction.
Source
Trends in Neurosciences. 29(12)(pp 695-703), 2006. Date of Publication: Dec 2006.
Abstract
Cocaine addiction is characterized by compulsive drug-taking behavior and high rates of
relapse. According to recent theories, this addiction is due to drug-induced adaptations in the
cellular mechanisms that underlie normal learning and memory. Such mechanisms involve
signaling by extracellular signal-regulated kinase (ERK). As we review here, evidence from
rodent studies also implicates ERK in cocaine psychomotor sensitization, cocaine reward,
consolidation and reconsolidation of memories for cocaine cues, and time-dependent
increases in cocaine seeking after withdrawal (incubation of cocaine craving). The role of
ERK in these behaviors involves long-term stable alterations in synaptic plasticity that result
from repeated cocaine exposure, and also rapidly induced alterations in synaptic transmission
events that acutely control cocaine-seeking behaviors. Pharmacological manipulations that
decrease the extent to which cocaine and cocaine cues induce ERK activity might therefore
be considered as potential treatments for cocaine addiction.
ISSN 0166-2236
Publication Type Journal: Review
Journal Name Trends in Neurosciences
Volume 29
Issue Part 12
Page 695-703
Year of Publication 2006
Date of Publication Dec 2006
COCAINE (A) 2006 <468>
Database EMBASE
Accession Number 2006565550
Authors Willuhn I. Steiner H.
Institution
(Willuhn, Steiner) Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine
and Science, Chicago Medical School, North Chicago, IL, United States.
(Steiner) Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and
Science, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, United States.
Country of Publication
United Kingdom
Title
Motor-skill learning-associated gene regulation in the striatum: Effects of cocaine.
Source
Neuropsychopharmacology. 31(12)(pp 2669-2682), 2006. Date of Publication: 04 Dec 2006.
Abstract
Psychostimulant-induced molecular changes in cortico-basal ganglia-cortical circuits play a
critical role in addiction and dependence. These changes include alterations in gene
regulation particularly in projection neurons of the sensorimotor striatum. We previously
showed that cocaine-induced gene regulation in such neurons is dependent on the behavior
performed during drug action. Rats trained on a running wheel under the influence of cocaine
for 4 days subsequently displayed greater c-fos induction by cocaine than untrained controls.
This effect was selective for the sensorimotor striatum, which is known to mediate forms of
motor learning. In the present study, we investigated whether this enhanced cellular
responsiveness was associated with learning of wheel running or with prolonged running
(exercising), by assessing c-fos inducibility after 1, 2, or 8 days of training. Wheel training was
performed after injection of cocaine (25 mg/kg) or vehicle, and c-fos induction by a cocaine
challenge was measured 24 h later. Rats that trained under cocaine (but not vehicle) showed
a greater c-fos response in the striatum compared to locked-wheel controls. This effect was
present after the 1-day training, peaked after 2 days, and dissipated by 8 days of training.
Similar effects were found for substance P, but not enkephalin, expression. These changes in
striatal gene regulation paralleled improvement in wheel running, which was facilitated by
cocaine. Thus, these training-induced molecular changes do not appear to represent
exercising effects, but may reflect motor learning-associated neuronal changes altered by
cocaine. Such cocaine effects may contribute to aberrant motor learning implicated in
psychostimulant addiction. copyright 2006 Nature Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 31
Issue Part 12
Page 2669-2682
Year of Publication 2006
Date of Publication 04 Dec 2006
COCAINE (A) 2006 <469>
Database EMBASE
Accession Number 2006565549
Authors Ferguson S.M. Fasano S. Yang P. Brambilla R. Robinson T.E.
Institution
(Ferguson, Robinson) Neuroscience Program, University of Michigan, Ann Arbor, MI, United States.
(Fasano, Brambilla) San Raffaele Research Institute and University, Milano, Italy.
(Fasano) Istituto di Psicologia, Facolta di Medicina, Universita degli Studi di Milano, Milano, Italy.
(Yang, Robinson) Department of Psychology, University of Michigan, Ann Arbor, MI, United States.
(Robinson) Department of Psychology (Biopsychology), University of Michigan, East Hall, 525 East University
Avenue, Ann Arbor, MI 48109-1109, United States.
Country of Publication
United Kingdom
Title
Knockout of ERK1 enhances cocaine-evoked immediate early gene expression and
behavioral plasticity.
Source
Neuropsychopharmacology. 31(12)(pp 2660-2668), 2006. Date of Publication: 04 Dec 2006.
Abstract
The ability of cocaine to produce lasting neural adaptations in mesocorticolimbic brain
regions is thought to promote drug seeking and facilitate addiction in humans. The Rascontrolled Raf-MEK-ERK protein kinase signaling cascade has been implicated in the
behavioral and neurobiological actions of cocaine in animals. However, these
pharmacological studies have not been able to determine the specific role of the two
predominant isoforms of ERK (ERK1 and ERK2) in these processes. We report here that
deletion of the ERK1 isoform, which leads to increased ERK2 stimulus-dependent signaling,
facilitates the development of cocaine-induced psychomotor sensitization and the acquisition
of a cocaine conditioned place preference. Conversely, pharmacological blockade of ERK
signaling attenuates the development of psychomotor sensitization to cocaine. Finally,
cocaine-evoked gene expression in mesocorticolimbic brain regions is potentiated in ERK1deficient mice. Thus, alterations in ERK signaling influence both the neurobiological impact of
cocaine and its ability to produce enduring forms of drug experience-dependent behavioral
plasticity. Our results suggest that enhanced ERK2 signaling following repeated drug
exposure may facilitate the development of forms of cocaine-induced plasticity that contribute
to addiction. copyright 2006 Nature Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 31
Issue Part 12
Page 2660-2668
Year of Publication 2006
Date of Publication 04 Dec 2006
COCAINE (A) 2006 <471>
Database EMBASE
Accession Number 2006564363
Authors Malison R.T. Kranzler H.R. Yang B.-Z. Gelernter J.
Institution
(Malison, Yang, Gelernter) Department of Psychiatry, Division of Human Genetics, Yale University School of
Medicine,
(Malison) Ribicoff Research Facilities, Connecticut Mental Health Center,
(Kranzler) Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States.
(Yang, Gelernter) VA Connecticut, West Haven, CT, United States.
(Malison) Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, 34 Park Street, New
Haven, CT 06519, United States.
Country of Publication
United Kingdom
Title
Human clock, PER1 and PER2 polymorphisms: Lack of association with cocaine
dependence susceptibility and cocaine-induced paranoia.
Source
Psychiatric Genetics. 16(6)(pp 245-249), 2006. Date of Publication: Dec 2006.
Abstract
Considerable research points to the importance of genetic mechanisms in psychostimulant
addiction. Behavioral sensitization, a well-documented response to repeated stimulant
exposure, may be mechanistically important in clinical features of the disorder, including
escalating patterns of drug use, craving and drug-induced paranoia. Basic studies in both
Drosophila melanogaster and mice have suggested the importance of circadian rhythm genes
in locomotor sensitization and reward. The primary objective of the current study was to
assess the potential involvement of three human orthologs (CLOCK, PER1 and PER2) in
clinical phenotypes of the disorder. Allelic associations of three single nucleotide
polymorphisms (SNPs) were assessed for both cocaine dependence and cocaine-induced
paranoia in 186 cases and 273 controls. Potential population stratification biases were
controlled for by means of within-population comparisons, and by structured association
methods (using all populations). No differences in allele frequencies were found for any of the
three single nucleotide polymorphisms studied between cocaine dependent and control
subjects or between paranoid and nonparanoid cocaine users. These results do not support
the involvement of genetic variation in these three circadian gene SNPs for influencing risks
for either of these cocaine phenotypes. copyright 2006 Lippincott Williams & Wilkins, Inc.
ISSN 0955-8829
Publication Type Journal: Article
Journal Name Psychiatric Genetics
Volume 16
Issue Part 6
Page 245-249
Year of Publication 2006
Date of Publication Dec 2006
COCAINE 2006 <474>
Database EMBASE
Accession Number 2006556697
Authors Rothman R.B. Blough B.E. Baumann M.H.
Institution
(Rothman, Baumann) Clinical Psychopharmacology Section Intramural Research Program, National Institute on
Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, United States.
(Blough) Chemistry and Life Sciences Group, Research Triangle Institute International, Research Triangle Park, NC
27709, United States.
Country of Publication
United Kingdom
Title
Dual dopamine-5-HT releasers: potential treatment agents for cocaine addiction.
Source
Trends in Pharmacological Sciences. 27(12)(pp 612-618), 2006. Date of Publication: Dec
2006.
Abstract
Biogenic amine transporters (BATs) are integral membrane proteins that translocate
biogenic amine neurotransmitters [norepinephrine, dopamine (DA) and 5-hydroxytryptamine
(5-HT)] across cell membranes. BATs are the principal sites of action for many psychotropic
drugs, including abused stimulants such as cocaine and methamphetamine. Preclinical and
human data demonstrate that withdrawal from long-term cocaine administration produces a
dual deficit of synaptic DA and 5-HT in the brain, indicating the advantage of developing
medications that normalize impairments in both neurotransmitter systems. In this article, we
review data supporting the notion that stimulant effects normally produced by increased levels
of extracellular DA can be antagonized by concurrent increases in levels of extracellular 5-HT.
Accordingly, nonselective BAT substrates that can release both DA and 5-HT, such as the
novel compound PAL287, have low abuse potential while maintaining the ability to suppress
drug-seeking behavior. The collective findings indicate that such drugs will provide
neurochemical normalization therapy for cocaine addiction and might also be useful for
treating depression, obsessive-compulsive disorder, attention deficit disorder and obesity.
ISSN 0165-6147
Publication Type Journal: Article
Journal Name Trends in Pharmacological Sciences
Volume 27
Issue Part 12
Page 612-618
Year of Publication 2006
Date of Publication Dec 2006
COCAINE 2006 <478>
Database EMBASE
Accession Number 2006545651
Authors Harper S.J. Jones N.S.
Institution
(Harper, Jones) Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Nottingham NG7
2UH, United Kingdom.
Country of Publication
United Kingdom
Title
Cocaine: What role does it have in current ENT practice? A review of the current
literature.
Source
Journal of Laryngology and Otology. 120(10)(pp 808-811), 2006. Date of Publication: Oct
2006.
Abstract
Topical cocaine is used by many otorhinolaryngologists because of its good local
anaesthetic and vasoconstrictive properties. A review of the available literature suggests a
risk/benefit analysis would suggest that in the out-patient setting local anaesthetic agents
which do not contain cocaine should be used. For rhinosurgical procedures, preparations
containing cocaine and adrenaline in the appropriate concentrations and doseage are safe in
the vast majority of patients without previous cardiac disease. The relative benefit of using
cocaine in relation to other topical analgesics and vasoconstrictors in surgery remains
unproven and alternative preparations should be used wherever there is concern over the
cardiac status of the patient. It is important to be alert to the possibility that patients
presenting with a septal perforation or destructive midfacial lesions may be suffering from an
addiction to cocaine. It is important to arrive at the correct diagnosis in a destructive process
and even in the presence of raised antineutrophilic cytoplasmic antibodies (ANCA) a
diagnosis of cocaine abuse should actively be excluded. copyright 2006 JLO (1984) Limited.
ISSN 0022-2151
Publication Type Journal: Review
Journal Name Journal of Laryngology and Otology
Volume 120
Issue Part 10
Page 808-811
Year of Publication 2006
Date of Publication Oct 2006
COCAINE 2006 <535>
Database EMBASE
Accession Number 2006464582
Authors Pollandt S. Liu J. Orozco-Cabal L. Grigoriadis D.E. Vale W.W. Gallagher J.P. Shinnick-Gallagher P.
Institution
(Pollandt, Liu, Orozco-Cabal, Gallagher, Shinnick-Gallagher) University of Texas, Medical Branch, Department of
Pharmacology and Toxicology, Galveston, TX 77555-1031, United States.
(Grigoriadis) Neurocrine Biosciences Incorporated, 12790 El Camino Real, San Diego, CA 92130, United States.
(Vale) Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, Peptide Biology
Laboratory, 10010 N. Torrey Pines Road, San Diego, CA 92037, United States.
Country of Publication
United Kingdom
Title
Cocaine withdrawal enhances long-term potentiation induced by corticotropinreleasing factor at central amygdala glutamatergic synapses via CRF₁,
NMDA receptors and PKA.
Source
European Journal of Neuroscience. 24(6)(pp 1733-1743), 2006. Date of Publication: Sep
2006.
Abstract
Cocaine addiction is an enduring, relapsing, behavioural disorder in which stressors
reinstate cocaine-seeking even after prolonged abstinence. Evidence suggests that the
'anxiety-like' behaviour and stress associated with protracted withdrawal may be mediated by
increased corticotropin-releasing factor (CRF) in the central nucleus of the amygdala (CeA), a
part of the limbic circuitry engaged in the coding and transmission of stimulus-reward
associations. In the present study we describe a long-lasting potentiation of glutamatergic
transmission induced at lateral amygdala (LA)-to-CeA synapses by rat/human CRF. After 2
weeks of withdrawal from repeated intermittent exposure to cocaine, CRF-induced long-term
potentiation (LTP) was greatly enhanced compared to the respective saline control group
while, after short-term withdrawal (24 h), there was no significant difference between the two
treatment groups, indicating alterations in CRF systems during protracted withdrawal from
chronic cocaine. After prolonged withdrawal, CRF-induced LTP was dependent on activation
of CRF₂, Ca_V2.3 (R-type) calcium channels and intracellular
signalling through protein kinase C in both saline- and cocaine-treated groups. The enhanced
CRF-induced LTP after 2 weeks of withdrawal was mediated through augmented
CRF₁ receptor function, associated with an increased signalling through protein
kinase A, and required N-methyl-d-aspartate (NMDA) receptors. Accordingly, single-cell
recordings revealed a significantly increased NMDA/AMPA ratio after prolonged withdrawal
from the cocaine treatment. These results support a role for CRF₁ receptor
antagonists as plausible treatment options during withdrawal from chronic cocaine and
suggest Ca_V2.3 blockers as potential candidates for pharmaceutical modulation
of CRF systems. copyright The Authors (2006).
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 24
Issue Part 6
Page 1733-1743
Year of Publication 2006
Date of Publication Sep 2006
COCAINE (A) 2006 <540>
Database EMBASE
Accession Number 2006461350
Authors Hummel M. Schroeder J. Liu-Chen L.-Y. Cowan A. Unterwald E.M.
Institution
(Hummel, Schroeder, Liu-Chen, Cowan, Unterwald) Department of Pharmacology, the Center for Substance Abuse
Research, Temple University School of Medicine, Philadelphia, PA 19140, United States.
(Unterwald) Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10021,
United States.
Country of Publication
United Kingdom
Title
An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaineinduced behavioral sensitization and reward in mice.
Source
Neuroscience. 142(2)(pp 481-491), 2006. Date of Publication: 13 Oct 2006.
Abstract
Numerous studies support a role for the endogenous opioid system in cocaine-influenced
behavior. Few of these studies, however, selectively delineate a role for the mu opioid
receptor (MOR) in this regard. This investigation examined if the MOR modulates cocaineinduced behavior in mice using a 17-base antisense oligodeoxynucleotide (AS ODN) directed
against the MOR coding sequence 16-32. Specifically, cocaine-induced behavioral
sensitization and conditioned reward were investigated. For the sensitization study, C57BL/6J
mice received eight intermittent i.c.v. infusions of saline, mismatch oligodeoxynucleotide
(ODN) (20 mug/4 mul) or AS ODN (20 mug/4 mul) over 20 days. Mice also received
concomitant once daily i.p. injections of saline (4 ml/kg) or cocaine (15 mg/kg) for 10 days.
There was a 7-day withdrawal period, after which all mice were challenged with cocaine (15
mg/kg) to test for behavioral sensitization. For the conditioned place preference (CPP) study,
mice received five i.c.v. infusions of mismatch ODN or MOR AS ODN (days 1-5). An unbiased
counterbalanced conditioning procedure was used where mice were conditioned with saline
(4 ml/kg, i.p.) and cocaine (15 mg/kg, i.p.) on alternate days for four sessions (days 3-6). Mice
were tested on day 7 for CPP. Immediately following testing, [³H]DAMGO (dAla², N-Me-Phe⁴, Gly-ol⁵-enkephalin) receptor
binding to brain homogenates was conducted. MOR AS attenuated cocaine-induced
behavioral sensitization and conditioned reward. MOR AS ODN also reduced
[³H]DAMGO binding. Collectively, these findings implicate the MOR as playing
an important neuromodulatory role in the behavioral effects of cocaine in mice. copyright 2006
IBRO.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 142
Issue Part 2
Page 481-491
Year of Publication 2006
Date of Publication 13 Oct 2006
COCAINE (A) 2006 <543>
Database EMBASE
Accession Number 2006460042
Authors Schank J.R. Ventura R. Puglisi-Allegra S. Alcaro A. Cole C.D. Liles L.C. Seeman P. Weinshenker D.
Institution
(Schank, Cole, Liles, Weinshenker) Department of Human Genetics, Emory University, Atlanta, GA, United States.
(Ventura, Puglisi-Allegra, Alcaro) Dipartimento di Psicologia, Universit La Sapienza, Rome, Italy.
(Ventura, Puglisi-Allegra, Alcaro) Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, Rome,
Italy.
(Cole) Center for Behavioral Neuroscience, Emory University, Atlanta, GA, United States.
(Seeman) Department of Pharmacology, University of Toronto, Toronto, Ont., Canada.
(Weinshenker) Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta,
GA 30322, United States.
Country of Publication
United Kingdom
Title
Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling
and are hypersensitive to cocaine.
Source
Neuropsychopharmacology. 31(10)(pp 2221-2230), 2006. Date of Publication: 07 Oct 2006.
Abstract
Multiple lines of evidence demonstrate that the noradrenergic system provides both direct
and indirect excitatory drive onto midbrain dopamine (DA) neurons. We used DA betahydroxylase (DBH) knockout (Dbh-/-) mice that lack norepinephrine (NE) to determine the
consequences of chronic NE deficiency on midbrain DA neuron function in vivo. Basal
extracellular DA levels were significantly attenuated in the nucleus accumbens (NAc) and
caudate putamen (CP), but not prefrontal cortex (PFC), of Dbh-/- mice, while amphetamineinduced DA release was absent in the NAc and attenuated in the CP and PFC. The decrease
in dopaminergic tone was associated with a profound increase in the density of high-affinity
state D₁ and D₂ DA receptors in the NAc and CP, while DA
receptors in the PFC were relatively unaffected. As a behavioral consequence of these
neurochemical changes, Dbh-/- mice were hypersensitive to the psychomotor, rewarding, and
aversive effects of cocaine, as measured by locomotor activity and conditioned place
preference. Antagonists of DA, but not 5-HT, receptors attenuated the locomotor
hypersensitivity to cocaine in Dbh-/- mice. As DBH activity in humans is genetically controlled
and the DBH inhibitor disulfiram has shown promise as a pharmacotherapy for cocaine
dependence, these results have implications for the influence of genetic and pharmacological
DBH inhibition on DA system function and drug addiction. copyright 2006 Nature Publishing
Group. All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 31
Issue Part 10
Page 2221-2230
Year of Publication 2006
Date of Publication 07 Oct 2006
COCAINE 2006 <573>
Database EMBASE
Accession Number 2006439039
Authors Patkar A.A. Mannelli P. Hill K.P. Peindl K. Pae C.-U. Lee T.H.
Institution
(Patkar, Mannelli, Peindl, Pae, Lee) Department of Psychiatry and Behavioral Sciences, Duke University, 4323 Ben
Franklin Boulevard, Durham, NC 27704, United States.
(Hill) Department of Medicine, Yale University, New Haven, CT, United States.
Country of Publication
United Kingdom
Title
Relationship of prolactin response to meta-chlorophenylpiperazine with severity of
drug use in cocaine dependence.
Source
Human Psychopharmacology. 21(6)(pp 367-375), 2006. Date of Publication: Aug 2006.
Abstract
Rationale: Serotonergic (5-HT) mechanisms appear to mediate central effects of cocaine.
Therefore 5-HT disturbances could be associated with drug severity. Objectives: We
investigated whether prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a
mixed 5-HT agonist/antagonist were associated with severity of cocaine use. Methods: Thirtysix cocaine-dependent subjects and 33 controls underwent a challenge with 0.5 mg/kg of oral
m-CPP. Severity of drug use was assessed using the Addiction Severity Index (ASI). Results:
The PRL response to m-CPP was significantly blunted in cocaine patients compared to
controls (F = 21.86, p < 0.001). DeltaPRL (peak PRL - baseline PRL) was negatively
correlated with ASI-drug (r = -0.45, p < 0.01), ASI-alcohol (r = -0.32, p < 0.05), and ASIpsychological (r = -0.41, p < 0.01) composite scores, and with the quantity, frequency and
duration of drug use (r ranged from - 0.41 to - 0.32, p ranged from < 0.01 to 0.05).
Hierarchical regressions showed that ASI-drug composite scores significantly predicted the
variance in DeltaPRL after controlling for behavioral and demographic variables (F = 4.27, p <
0.05). Conclusions: The results indicate that disturbances in 5-HT function as reflected by a
blunted response to m-CPP seem to be primarily associated with severity of drug use and to
a lesser, although significant extent with behavioral traits in cocaine-dependent patients.
Copyright copyright 2006 John Wiley & Sons, Ltd.
ISSN 0885-6222
Publication Type Journal: Article
Journal Name Human Psychopharmacology
Volume 21
Issue Part 6
Page 367-375
Year of Publication 2006
Date of Publication Aug 2006
COCAINE 2006 <593>
Database EMBASE
Accession Number 2006400894
Authors Mcgeehan A.J. Olive M.F.
Institution
(Mcgeehan) Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San
Francisco, Emeryville, CA, United States.
(Olive) Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical
University of South Carolina, Charleston, SC, United States.
(Olive) Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical
University of South Carolina, 67 President Street, Charleston, SC 29425, United States.
Country of Publication
United Kingdom
Title
Attenuation of cocaine-induced reinstatement of cocaine conditioned place
preference by acamprosate.
Source
Behavioural Pharmacology. 17(4)(pp 363-367), 2006. Date of Publication: Jun 2006.
Abstract
Acamprosate (calcium acetylhomotaurinate) is a glutamatergic neuromodulator efficacious
at reducing relapse in alcoholic patients. The effect of acamprosate on relapse to other drugs
of abuse has received little attention, however, and given increasing evidence that
glutamatergic transmission mediates relapse to cocaine-seeking behavior, the purpose of this
study was to assess the effects of acamprosate on the reinstatement of a conditioned place
preference for cocaine. Mice were conditioned daily with cocaine (15 mg/kg), tested for the
establishment of cocaine conditioned place preference, and then retested once weekly to
monitor the extinction of the place preference. Following extinction of cocaine conditioned
place preference, animals were treated daily with saline or acamprosate (30 or 100 mg/kg) for
3 days, followed by a single injection of cocaine (15 mg/kg) to reinstate conditioned place
preference. In mice treated with saline or the low (30 mg/kg) dose of acamprosate, cocaine
induced a significant reinstatement of the previously extinguished conditioned place
preference; however, this reinstatement was not observed in mice treated with the high (100
mg/kg) dose of acamprosate. These results indicate that acamprosate can attenuate relapselike behavior in mice and suggest that this compound may be potentially useful in the
treatment for cocaine addiction. copyright 2006 Lippincott Williams & Wilkins.
ISSN 0955-8810
Publication Type Journal: Article
Journal Name Behavioural Pharmacology
Volume 17
Issue Part 4
Page 363-367
Year of Publication 2006
Date of Publication Jun 2006
COCAINE (A) 2006 <682>
Database EMBASE
Accession Number 2006291876
Authors Xi Z.-X. Newman A.H. Gilbert J.G. Pak A.C. Peng X.-Q. Ashby Jr. C.R. Gitajn L. Gardner E.L.
Institution
(Xi, Gilbert, Pak, Peng, Gitajn, Gardner) Neuropsychopharmacology Section, National Institute on Drug Abuse,
National Institutes of Health, Baltimore, MD, United States.
(Newman) Medicinal Chemistry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore,
MD, United States.
(Ashby Jr.) Department of Pharmaceutical Sciences, Saint John's University, Jamaica, NY, United States.
(Xi) Neuropsychopharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug
Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, United States.
Country of Publication
United Kingdom
Title
The novel dopamine D₃ receptor antagonist NGB 2904 inhibits cocaine's
rewarding effects and cocaine-induced reinstatement of drug-seeking behavior in rats.
Source
Neuropsychopharmacology. 31(7)(pp 1393-1405), 2006. Date of Publication: 19 Jul 2006.
Abstract
Accumulating evidence indicates that dopamine (DA) D₃ receptor antagonists
appear highly promising in attenuating cocaine reward and relapse in preclinical models of
addiction. In the present study, we investigated the effects of the novel D₃selective
antagonist
NGB
2904
(N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-3fluorenylcarboxamide) on cocaine self-administration, cocaine-enhanced brain stimulation
reward (BSR), and cocaine-triggered reinstatement of drug-seeking behavior in male LongEvans rats. We found that: (1) acute intraperitoneal (i.p.) administration of NGB 2904 (0.1-10
mg/kg) failed to alter cocaine self-administration (0.5 mg/kg/infusion) under fixed-ratio 2 (FR2)
reinforcement, but 1 or 5 mg/kg NGB 2904 significantly lowered the break-point for cocaine
self-administration under progressive-ratio (PR) reinforcement; (2) cocaine (1, 2, and 10
mg/kg) significantly enhanced electrical BSR (decreased brain reward thresholds), while NGB
2904 significantly inhibited the enhancement of BSR elicited by 2 mg/kg, but not 10 mg/kg of
cocaine; (3) NGB 2904 alone neither maintained self-administration behavior nor altered brain
reward thresholds; and (4) NGB 2904 significantly inhibited cocaine-triggered reinstatement of
extinguished
drug-seeking
behavior,
but
not
sucrose-plus-sucrose-cue-triggered
reinstatement of sucrose-seeking behavior. Overall, these data show that the novel D
₃-selective antagonist NGB 2904 attenuates cocaine's rewarding effects as
assessed by PR self-administration, BSR, and cocaine-triggered reinstatement of cocaineseeking behavior. Owing to these properties and to its lack of rewarding effects (as assessed
by BSR and by substitution during drug self-administration), NGB 2904 merits further
investigation as a potential agent for treatment of cocaine addiction. copyright 2006 Nature
Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 31
Issue Part 7
Page 1393-1405
Year of Publication 2006
Date of Publication 19 Jul 2006
COCAINE 2006 <686>
Database EMBASE
Accession Number 2006282712
Authors Komokata T. Nishida S. Ganz S. Levi D.M. Fukumori T. Tzakis A.G.
Institution
(Komokata) Department of Hepato-Biliary-Pancreatic Surgery, Kagoshima University Graduate School of Medical
and Dental Science, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
(Komokata, Nishida, Ganz, Levi, Fukumori, Tzakis) Department of Surgery, Division of Transplantation, University of
Miami School of Medicine, Miami, FL, United States.
Country of Publication
United Kingdom
Title
The impact of donor cocaine use on the outcome of adult liver transplantation.
Source
Clinical Transplantation. 20(3)(pp 295-300), 2006. Date of Publication: May 2006.
Abstract
Backgrounds: To investigate the feasibility of adult liver transplantation from donors with
cocaine use. Methods: Of 807 adult liver transplantations performed between 1994 and 2000,
72 donors (8.9%) were current cocaine users. Donor characteristics and post-transplantation
outcomes were retrospectively compared between the 72 cocaine and 126 control group
selected from the remaining 735 donors, matched for age and having no history of drug use.
Results: Marijuana, opiates and amphetamines were drugs of abuse often present with
cocaine. Except for a high incidence of acute alcohol use in the cocaine donors, donor
characteristics were comparable. The cocaine group had a significantly higher graft loss
within three months of transplant (18.1% vs. 7.9%, p<0.05), and had a trend toward lower
graft survival (76% vs. 86% at one yr). Conclusions: Potential adverse effect of cocaine and
substances concurrently involved on donor liver was suggested. To clarify the distinct
acceptance criteria of cocaine users for liver donation, prospective study is warranted.
copyright 2006 Blackwell Munksgaard.
ISSN 0902-0063
Publication Type Journal: Article
Journal Name Clinical Transplantation
Volume 20
Issue Part 3
Page 295-300
Year of Publication 2006
Date of Publication May 2006
COCAINE (A) 2006 <716>
Database EMBASE
Accession Number 2006257085
Authors Bradberry C.W. Rubino S.R.
Institution
(Bradberry, Rubino) Department of Psychiatry, University of Pittsburgh, 3025 E. Carson St., Pittsburgh, PA 15203,
United States.
Country of Publication
United Kingdom
Title
Dopaminergic responses to self-administered cocaine in Rhesus monkeys do not
sensitize following high cumulative intake.
Source
European Journal of Neuroscience. 23(10)(pp 2773-2778), 2006. Date of Publication: May
2006.
Abstract
Sensitization of mesolimbic dopamine (DA) systems by administration of psychostimulants
has been observed repeatedly in rodents. This phenomenon has been incorporated into
theories of neurobiological adaptation underlying addiction, and is believed to be a
mechanism whereby drug-associated cues acquire the ability to control behaviour via a
conditioned release of DA. However, we have previously demonstrated in nonhuman
primates that drug cues that cause cocaine seeking do not promote a conditioned increase in
DA release of sufficient endurance to be measured in 2-min samples. In addition, imaging
studies in humans and nonhuman primates that have been chronically exposed to
psychostimulants have not demonstrated an increase in DA release upon psychostimulant
challenge. Here we report that following 32 weeks of self-administration by rhesus monkeys,
no increase over time in the DA response to self-administered cocaine was observed in any
striatal subregion or individual animal. These results are consistent with clinical imaging
studies showing a lack of DA sensitization, and might provide a mechanism to explain our
previous observation that the rodent and primate differ in neurochemical response to drugassociated cues. copyright The Authors (2006).
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 23
Issue Part 10
Page 2773-2778
Year of Publication 2006
Date of Publication May 2006
COCAINE 2006 <768>
Database EMBASE
Accession Number 2006188236
Authors Lambert N.M. McLeod M. Schenk S.
Institution
(Lambert, McLeod) University of California at Berkeley, Berkeley, CA, United States.
(Schenk) Victoria University, Wellington, New Zealand.
(Lambert) Graduate School of Education, Cognition and Development, University of California at Berkeley,
Berkeley, CA 94720-1670, United States.
Country of Publication
United Kingdom
Title
Subjective responses to initial experience with cocaine: An exploration of the
incentive-sensitization theory of drug abuse.
Source
Addiction. 101(5)(pp 713-725), 2006. Date of Publication: May 2006.
Abstract
Aims: This study investigated the relationship between positive and negative subjective
responses at the time of initial cocaine use with adult cocaine dependence and life-time use
rates. Psychostimulant pre-exposure, regular smoking or stimulant treatment before initiation
were examined to explore the incentive sensitization theory of addiction. Participants: A total
of 202 adult participants who had tried cocaine on at least one occasion were studied
prospectively from childhood into adulthood. The cocaine-initiated group included 89 who met
Diagnostic and Statistical Manual version IV (DSM-IV) criteria for attention deficit hyperactive
disorder (ADHD) and 113 age-matched controls. Design: Five childhood and three adulthood
interviews provided data on ages of initiation into cocaine and life-time use of cocaine from
ages 16-40 years. Correlations of each subjective response and analyses of variance
(ANOVAs) of cocaine 'liking' and 'wanting' with DSM-III-R cocaine dependence and life-time
use provided support for the validity of the measures. ANOVA provided evidence of the effect
of psychostimulant pre-exposure on 'liking' and 'wanting'. Logistic regression modeled the
prediction of dependence and life-time use with the independent variables of 'liking' and
'wanting', psychostimulant pre-exposure and participant characteristics. Results: When
cocaine was first tried, 'liking' and 'wanting' were significant predictors of cocaine dependence
and life-time use. Mean 'liking' or 'wanting' responses did not differ by participant
characteristics. Those who were pre-exposed by regular smoking or stimulant treatment had
higher 'liking' and 'wanting' scores; but participants who were pre-exposed by both stimulant
treatment and regular smoking reported the lowest liking and the highest wanting responses,
consistent with the incentive sensitization theory. Logistic regression showed that the 'liking'
and 'wanting' responses increased significantly the odds of DSM-III-R cocaine dependence
and life-time use. Conclusion: In this sample, subjective 'liking' and 'wanting' measured risk
for cocaine abuse. copyright 2006 Society for the Study of Addiction.
ISSN 0965-2140
Publication Type Journal: Article
Journal Name Addiction
Volume 101
Issue Part 5
Page 713-725
Year of Publication 2006
Date of Publication May 2006
COCAINE 2006 <822>
Database EMBASE
Accession Number 2006142100
Authors Sofuoglu M. Kosten T.R.
Institution
(Sofuoglu, Kosten) Yale University, School of Medicine, Department of Psychiatry, 950 Campbell Ave., West Haven,
CT 06516, United States.
Country of Publication
United Kingdom
Title
Emerging pharmacological strategies in the fight against cocaine addiction.
Source
Expert Opinion on Emerging Drugs. 11(1)(pp 91-98), 2006. Date of Publication: Mar 2006.
Abstract
Cocaine addiction continues to be an important public health problem worldwide. At present,
there are no proven pharmacotherapies for cocaine addiction. The studies reviewed here
revealed a number of emerging targets for cocaine pharmacotherapy. First, disulfiram, a
medication with dopaminergic effects, reduced cocaine use in a number of clinical trials.
Second, GABA medications, tiagabine and topiramate, were found promising in clinical trials.
Third, a beta-adrenergic blocker, propranolol, may be effective especially among cocaineaddicted individuals with high withdrawal severity. Fourth, treatment with a stimulant
medication, modafinil, has reduced cocaine use. Last, a cocaine vaccine that slows entry of
cocaine into the brain holds promise. These promising findings need to be further tested in
controlled clinical trials. copyright 2006 Ashley Publications.
ISSN 1472-8214
Publication Type Journal: Review
Journal Name Expert Opinion on Emerging Drugs
Volume 11
Issue Part 1
Page 91-98
Year of Publication 2006
Date of Publication Mar 2006
COCAINE 2006 <833>
Database EMBASE
Accession Number 2006134052
Authors Ballon N. Leroy S. Roy C. Bourdel M.C. Charles-Nicolas A. Krebs M.O. Poirier M.F.
Institution
(Ballon, Roy, Charles-Nicolas) Department of Psychiatry, University Hospital of Fort de France, BP 632, 97221 Fort
de France, Martinique.
(Ballon, Leroy, Bourdel, Krebs, Poirier) INSERM E117, Universite Paris 5, SHU Hopital Sainte Anne, Paris, France.
Country of Publication
United Kingdom
Title
(AAT)n repeat in the cannabinoid receptor gene (CNR1): Association with cocaine
addiction in an African-Caribbean population.
Source
Pharmacogenomics Journal. 6(2)(pp 126-130), 2006. Date of Publication: Mar 2006.
Abstract
Owing to their agonist action on dopaminergic systems, cannabinoids may play a major role
in substance dependency and schizophrenia. We examined the (AAT)n triplet repeat
polymorphism nearby the CNR1 gene, which encodes human cannabinoid (CB1) receptor, in
a male Afro-Caribbean population. The allelic and genotypic distributions were significantly
different in non-schizophrenic cocaine dependents (n = 97), schizophrenic cocaine
dependents (n = 45) and matched controls (n = 88) (P<10^-4). The frequency of
the (AAT)12 repeat allele was increased in non-schizophrenic cocaine dependents and
schizophrenic cocaine dependents vs controls (25.3 and 26.7 vs 5.7%) (P < 10⁴). Our results support that the (AAT)n polymorphism nearby the CNR1 gene could be
associated with predisposition to cocaine dependency. copyright 2006 Nature Publishing
Group All rights reserved.
ISSN 1470-269X
Publication Type Journal: Article
Journal Name Pharmacogenomics Journal
Volume 6
Issue Part 2
Page 126-130
Year of Publication 2006
Date of Publication Mar 2006
COCAINE 2006 <835>
Database EMBASE
Accession Number 2006130937
Authors Goussakov I. Chartoff E.H. Tsvetkov E. Gerety L.P. Meloni E.G. Carlezon Jr. W.A. Bolshakov V.Y.
Institution
(Goussakov, Chartoff, Tsvetkov, Gerety, Meloni, Carlezon Jr., Bolshakov) Department of Psychiatry, McLean
Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, United States.
(Tsvetkov) Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St.
Petersburg, Russian Federation.
Country of Publication
United Kingdom
Title
LTP in the lateral amygdala during cocaine withdrawal.
Source
European Journal of Neuroscience. 23(1)(pp 239-250), 2006. Date of Publication: Jan 2006.
Abstract
The amygdala plays key roles in several aspects of addiction to drugs of abuse. This brain
structure has been implicated in behaviours that reflect drug reward, drug seeking, and the
aversive effects of drug withdrawal. Using a model that involves repeated cocaine injections
to approximate 'binge' intoxication, we show in rats that during cocaine withdrawal, the impact
of rewarding brain stimulation is attenuated, as quantified by alterations in intracranial selfstimulation (ICSS) behaviour. These behavioural signs of withdrawal are accompanied by
enhancements of glutamatergic synaptic transmission within the lateral amygdala (LA) that
occlude electrically induced long-term potentiation (LTP) in tissue slices. Synaptic
enhancements during periods of cocaine withdrawal are mechanistically similar to LTP
induced with electrical stimulation in control slices, as both forms of synaptic plasticity involve
an increase in glutamate release. These results suggest that mechanisms of LTP within the
amygdala are recruited during withdrawal from repeated exposure to cocaine. As such, they
raise the possibility that the development and maintenance of addictive behaviours may
involve, at least in part, mechanisms of synaptic plasticity within specific amygdala circuits.
copyright The Authors (2005).
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 23
Issue Part 1
Page 239-250
Year of Publication 2006
Date of Publication Jan 2006
COCAINE 2006 <911>
Database EMBASE
Accession Number 2006092238
Authors Ahmed S.H. Cador M.
Institution
(Ahmed, Cador) Laboratoire de Neuropsychobiologie des Desadaptations, University Victor-Segalen Bordeaux2,
Bordeaux, France.
(Ahmed) Laboratoire de Neuropsychobiologie des Desadaptations, CNRS-UMR 5541, University Victor-Segalen
Bordeaux2, 146 rue Leo-Saignat, Bordeaux 33076, France.
Country of Publication
United Kingdom
Title
Dissociation of psychomotor sensitization from compulsive cocaine consumption.
Source
Neuropsychopharmacology. 31(3)(pp 563-571), 2006. Date of Publication: Mar 2006.
Abstract
The transition from drug use to drug addiction is associated with a process of escalation,
whereby drug use becomes excessive and difficult to control. Several mechanisms have been
advanced to explain escalating patterns of drug use as opposed to nonescalating patterns.
Although current evidence favors hedonic tolerance, there remains some dispute about the
contribution of behavioral sensitization to cocaine intake escalation. Here, we concurrently
assessed the ability of cocaine to induce psychomotor sensitization and drug-seeking
behavior in animals with 1-h (short access or ShA) vs 6-h (long access or LgA) access to
intravenous (i.v.) cocaine self-administration. As expected, cocaine intake by LgA rats
escalated over time and became excessive compared to cocaine intake by ShA rats, which
remained low and stable. Despite escalated levels of cocaine consumption, however, LgA
rats were not more sensitized to cocaine than ShA rats. The dose - effect function for
cocaine-induced locomotion (0.125-1 mg, i.v.) was shifted to the left in LgA rats by the same
amount as in ShA rats after cocaine self-administration. In contrast, LgA rats were much more
responsive than ShA rats to the motivational effects of cocaine, as measured by the ability of
i.v. cocaine to reinstate extinguished drug-seeking behavior. This study demonstrates a
dissociation of psychomotor sensitization from the change in motivation underlying the
transition to compulsive cocaine consumption, and therefore suggests that responsiveness to
the motivational effects of the drug, not psychomotor sensitization, would represent a specific
behavioral marker of the transition to and maintenance of compulsive cocaine use. copyright
2006 Nature Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 31
Issue Part 3
Page 563-571
Year of Publication 2006
Date of Publication Mar 2006
COCAINE 2006 <916>
Database EMBASE
Accession Number 2006084773
Authors Morgan D. Liu Y. Roberts D.C.S.
Institution
(Morgan, Roberts) Department of Physiology and Pharmacology, Wake Forest University, School of Medicine,
Winston-Salem, NC, United States.
(Morgan, Liu, Roberts) Neuroscience Program, Wake Forest University, School of Medicine, Winston-Salem, NC,
United States.
(Morgan) Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, WinstonSalem, NC 27157, United States.
Country of Publication
United Kingdom
Title
Rapid and persistent sensitization to the reinforcing effects of cocaine.
Source
Neuropsychopharmacology. 31(1)(pp 121-128), 2006. Date of Publication: Jan 2006.
Abstract
The development of drug addiction involves a transition from recreational use to compulsive
drug seeking and taking, and this progression can occur rapidly with cocaine use. These data
highlight the importance of early drug exposure and the development of drug dependence;
however, little experimental attention has been paid to this phenomenon in animal models of
drug abuse. The present experiments demonstrate a progressive and rapid sensitization to
the reinforcing strength of cocaine assessed using a progressive ratio (PR) schedule in rats.
The first experiment found that rats show increased breakpoints over a 2-week period
following acquisition. Subsequent experiments examined the role of total cocaine intake
during the initial exposure period and found that low intakes (20 mg/ kg/day x 5 days) resulted
in sensitization, whereas relatively higher intake (60 or 100 mg/kg/day x 5 days) suppressed
the development of sensitization. In contrast, this higher level of intake (60 mg/kg/day x 5
days) only transiently suppressed the expression of sensitization. Examination of breakpoints
maintained by various doses of cocaine revealed an upward and leftward displacement of the
cocaine dose-effect curve, relative to nonsensitized animals. These studies describe a form of
sensitization that occurs rapidly to the reinforcing effects of cocaine, and provide a model to
study the potential impact of initial experience on the development of drug dependence.
copyright 2006 Nature Publishing Group All rights reserved.
ISSN 0893-133X
Publication Type Journal: Article
Journal Name Neuropsychopharmacology
Volume 31
Issue Part 1
Page 121-128
Year of Publication 2006
Date of Publication Jan 2006