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OPIOIDS 2009 / COCAINE 2009 <101> Database EMBASE Accession Number 0020180662 Authors Castells X. Kosten T.R. Capella D. Vidal X. Colom J. Casas M. Institution (Castells, Kosten, Capella, Vidal, Colom, Casas) Psychiatry Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain. Country of Publication United Kingdom Title Efficacy of opiate maintenance therapy and adjunctive interventions for opioid dependence with comorbid cocaine use disorders: A systematic review and metaanalysis of controlled clinical trials. Source The American journal of drug and alcohol abuse. 35(5)(pp 339-349), 2009. Date of Publication: 2009. Abstract AIMS: To determine the efficacy of Opiate Maintenance Therapy (OMT) and adjunctive interventions for dual heroin and cocaine dependence by means of a meta-analysis. METHOD: We searched for and retrieved randomized controlled clinical trials. We used RevMan 5.0 with random effects modeling for statistical analysis and for comparisons of relative risk, effect sizes, and confidence intervals. Subsequent moderator variables and sensitivity analyses were performed. RESULTS: Thirty-seven studies, which have enrolled 3,029 patients, have been included in this meta-analysis. High doses of OMT were more efficacious than lower ones in the achievement of sustained heroin abstinence (RR = 2.24 [1.54, 3.24], p < .0001) but had no effect on cocaine abstinence. At equivalent doses, methadone was more efficacious than buprenorphine on cocaine abstinence (RR = 1.63 [1.20, 2.22], p = .002) and also appeared to be superior on heroin abstinence (RR = 1.39 [1.00, 1.93], p = .05). Several pharmacological and psychological potentiation strategies have been investigated. An improvement on sustained cocaine abstinence was achieved with indirect dopaminergic agonists (RR = 1.44 [1.05, 1.98], p = .03) and with contingency management (CM) focusing on cocaine abstinence (RR = 3.11 [1.80, 5.35], p < .0001). CONCLUSIONS: Dual opioid and cocaine dependence can be effectively treated with OMT in combination with adjunctive interventions. Higher OMT doses are preferable to lower ones and methadone to buprenorphine. OMT can be enhanced with indirect dopaminergic drugs and with CM focusing on cocaine abstinence. Publication Type Journal: Article Journal Name The American journal of drug and alcohol abuse Volume 35 Issue Part 5 Page 339-349 Year of Publication 2009 Date of Publication 2009 COCAINE 2009 <661> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 20001286 Status MEDLINE Authors Small AC. Kampman KM. Plebani J. De Jesus Quinn M. Peoples L. Lynch KG. Authors Full Name Small, A C. Kampman, K M. Plebani, J. De Jesus Quinn, M. Peoples, L. Lynch, K G. Institution Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. Title Tolerance and sensitization to the effects of cocaine use in humans: a retrospective study of long-term cocaine users in Philadelphia. Source Substance Use & Misuse. 44(13):1888-98, 2009. Journal Name Substance Use & Misuse Country of Publication England Abstract In the effort to develop medications to combat addiction, researchers have developed models that attempt to describe the neurobiological process of cocaine dependence. It has not, however, yet been determined which of these models, if any, best fits the behaviors and experiences of patients. This project retrospectively evaluated changes in patients' experiences with cocaine over time in order to clarify the model that best fits clinical observations. In 2005 and 2007, 100 treatment-seeking, long-term cocaine users were recruited from an urban university-based treatment center in Philadelphia, PA, United States. Each participant was administered the "Cocaine History Questionnaire" which asked them to describe the initiation and escalation of their cocaine usage, changing reward perceptions, and effects of intoxication at certain points in their drug use careers. This data was then analyzed using repeated measures, examining the within subject differences in reported information over the time points. We found evidence that while the amount of drug used increases, self-reported euphoria decreases while negative symptoms associated with cocaine use also increase. The data provide preliminary evidence for the hedonic dysregulation model of addiction. Limitations and implications of the study are discussed in the conclusion. Publication Type Journal Article. Research Support, N.I.H., Extramural. Date of Publication 2009 Year of Publication 2009 Issue/Part 13 Volume 44 Page 1888-98 COCAINE <669> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 19874156 Status MEDLINE Authors Sanchez-Hervas E. Secades-Villa R. Jose Santonja Gomez F. Zacares Romaguera F. Garcia-Rodriguez O. Authors Full Name Sanchez-Hervas, Emilio. Secades-Villa, Roberto. Jose Santonja Gomez, Francisco. Zacares Romaguera, Francisco. Garcia-Rodriguez, Olaya. Institution UCA Catarroja. Dpt. 10. Valencia Regional Health Department, Valencia, Spain. Title Addictive severity in cocaine addicts measured with the EuropASI: differences between composite scores and severity ratings. Source American Journal on Addictions. 18(5):375-8, 2009 Sep-Oct. Journal Name American Journal on Addictions Country of Publication England Abstract In this study we present the addiction severity profile in a sample of 202 cocaine addicts, using the composite scores for each area of the EuropASI (European version of the ASI), which are compared with the severity ratings obtained through interviewers' subjective assessments. The results showed that the areas of the EuropASI which reflected the greatest severity according to the composite scores were, in the following order: employment/support, family/social situation, use of alcohol and psychiatric state. The results obtained with the composite scores show discrepancies with those obtained from the severity rating. Statistically significant differences were found in the areas of alcohol (Z = -6.205; p < 0.001), drugs (Z = -11.902; p < 0.001), family/social (Z = -6.915; p < 0.001) and psychiatric status (Z = -6.651; p < 0.001). The results call into question the reliability and validity of severity ratings obtained through interviewers' subjective assessments. For diagnosis and research, a more objective appraisal is recommended, using composite scores, since severity ratings depend totally on the interviewer's judgement, and do not appear to constitute a sound measure for estimating therapeutic change. Publication Type Comparative Study. Journal Article. Research Support, Non-U.S. Gov't. Date of Publication 2009 Sep-Oct Year of Publication 2009 Issue/Part 5 Volume 18 Page 375-8 COCAINE 2009 <133> DatabaseEMBASE Accession Number 2009128491 Authors Woicik P.A. Moeller S.J. Alia-Klein N. Maloney T. Lukasik T.M. Yeliosof O. Wang G.-J. Volkow N.D. Goldstein R.Z. Institution (Woicik, Alia-Klein, Maloney, Lukasik, Yeliosof, Wang, Goldstein) Brookhaven National Laboratory, Medical Department, Upton, NY, United States. (Moeller) Department of Psychology, University of Michigan, Ann Arbor, MI, United States. (Volkow) National Institute on Drug Abuse, Bethesda, MD, United States. (Woicik) Brookhaven National Laboratory, Medical Department, PO Box 5000, Upton, NY 11973-5000, United States. Country of Publication United Kingdom Title The neuropsychology of cocaine addiction: Recent cocaine use masks impairment. Source Neuropsychopharmacology. 34(5)(pp 1112-1122), 2009. Date of Publication: April 2009. Publisher Nature Publishing Group Abstract Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine. copyright 2009 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 34 Issue Part 5 Page 1112-1122 Year of Publication 2009 Date of Publication April 2009 COCAINE (A) 2009 <150> Database EMBASE Accession Number 2009076604 Authors Peng X.-Q. Ashby Jr. C.R. Spiller K. Li X. Li J. Thomasson N. Millan M.J. Mocaer E. Munoz C. Gardner E.L. Xi Z.-X. Institution (Peng, Spiller, Li, Li, Gardner, Xi) National Institute on Drug Abuse, Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, United States. (Ashby Jr.) Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, United States. (Thomasson, Mocaer, Munoz) Neuropsychiatry Department, Institut de Recherches Internationales Servier, 92615 Courbevoie, France. (Millan) Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, 78290 Croissy-sur-Seine, France. Country of Publication United Kingdom Title The preferential dopamine D3 receptor antagonist S33138 inhibits cocaine reward and cocaine-triggered relapse to drug-seeking behavior in rats. Source Neuropharmacology. 56(4)(pp 752-760), 2009. Date of Publication: March 2009. Publisher Elsevier Ltd Abstract We have previously reported that selective dopamine (DA) D3 receptor antagonists are effective in a number of animal models of drug addiction, but not in intravenous drug selfadministration, suggesting a limited ability to modify drug reward. In the present study, we evaluated the actions of S33138, a novel partially selective D3 receptor antagonist, in animal models relevant to drug addiction. S33138, at doses of 0.156 or 0.625 mg/kg (i.p.), attenuated cocaine-enhanced brain-stimulation reward (BSR), and the highest dose tested (2.5 mg/kg) produced a significant aversive-like rightward shift in BSR rate-frequency reward functions. Further, S33138 produced biphasic effects on cocaine self-administration, i.e., a moderate dose (2.5 mg/kg, p.o.) increased, while a higher dose (5 mg/kg, p.o.) inhibited, cocaine selfadministration. The increase in cocaine self-administration likely reflects a compensatory response to a partial reduction in drug reward after S33138. In addition, S33138 (0.156-2.5 mg/kg, p.o.) also dose-dependently inhibited cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-enhanced BSR and cocaine-triggered reinstatement produced by lower effective doses (e.g., 0.156 or 0.625 mg/kg) of S33138 is unlikely due to impaired locomotion, as lower effective doses of S33138 decreased neither Ymax levels in the BSR paradigm, rotarod performance, nor locomotion. However, the higher doses (2.5 or 5 mg/kg) of S33138 also significantly inhibited sucrose self-administration and rotarod performance, suggesting non-D3 receptor-mediated effects on non-drug reward and locomotion. These data suggest that lower doses of S33138 interacting essentially with D3 receptors have pharmacotherapeutic potential in treatment of cocaine addiction, while higher doses occupying D2 receptors may influence locomotion and non-drug reward. ISSN 0028-3908 Publication Type Journal: Article Journal Name Neuropharmacology Volume 56 Issue Part 4 Page 752-760 Year of Publication 2009 Date of Publication March 2009 COCAINE 2009 <153> Database EMBASE Accession Number 2009086572 Authors Hamilton J.D. Nguyen Q.X. Gerber R.M. Rubio N.B. Institution (Hamilton) Michael E. DeBakey VA Medical Center, Houston, TX, United States. (Hamilton) VA South Central Mental Illness Research, Education, and Clinical Center, Houston, TX, United States. (Hamilton) Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States. (Nguyen, Gerber, Rubio) Michael E. DeBakey VA Medical Center, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States. (Hamilton) Baylor College of Medicine, (Hamilton) 4413 Betty St., Bellaire, TX 77401, United States. Country of Publication United Kingdom Title Olanzapine in cocaine dependence: A double-blind, placebo-controlled trial. Source American Journal on Addictions. 18(1)(pp 48-52), 2009. Date of Publication: January 2009. Publisher Informa Healthcare Abstract Preclinical and uncontrolled human studies have suggested the possible efficacy of secondgeneration antipsychotics, particularly olanzapine, in treating cocaine dependence. We conducted a randomized, double-blind, placebo-controlled trial in which 48 cocainedependent subjects received olanzapine or identical-appearing placebo for 16 weeks. The primary outcome measure was the proportion of cocaine-negative weekly urine screens during treatment. Secondary measures included scores on a Craving Questionnaire, Addiction Severity Index subscales, and extrapyramidal symptom scales. Olanzapine and placebo did not differ on any outcome measure. Both olanzapine and placebo subjects frequently reported side effects, but no unexpected ones. We conclude that olanzapine appears ineffective for cocaine dependence. Copyright copyright American Academy of Addiction Psychiatry. ISSN 1055-0496 Publication Type Journal: Article Journal Name American Journal on Addictions Volume 18 Issue Part 1 Page 48-52 Year of Publication 2009 Date of Publication January 2009 COCAINE 2009 <194> Database EMBASE Accession Number 2009008514 Authors Heberlein U. Tsai L.T.-Y. Kapfhamer D. Lasek A.W. Institution (Heberlein, Tsai) Department of Anatomy, Program in Neuroscience, University of California at San Francisco, 1550 4th Street, Rock Hall, Mission Bay Campus, San Francisco, CA 94143-2324, United States. (Heberlein, Kapfhamer, Lasek) Ernest Gallo Clinic, Research Center, 5858 Horton Street, Suite 200, Emeryville, CA 94112, United States. Country of Publication United Kingdom Title Drosophila, a genetic model system to study cocaine-related behaviors: A review with focus on LIM-only proteins. Source Neuropharmacology. 56(SUPPL. 1)(pp 97-106), 2009. Date of Publication: 2009. Publisher Elsevier Ltd Abstract In the last decade, the fruit fly Drosophila melanogaster, highly accessible to genetic, behavioral and molecular analyses, has been introduced as a novel model organism to help decipher the complex genetic, neurochemical, and neuroanatomical underpinnings of behaviors induced by drugs of abuse. Here we review these data, focusing specifically on cocaine-related behaviors. Several of cocaine's most characteristic properties have been recapitulated in Drosophila. First, cocaine induces motor behaviors in flies that are remarkably similar to those observed in mammals. Second, repeated cocaine administration induces behavioral sensitization a form of behavioral plasticity believed to underlie certain aspects of addiction. Third, a key role for dopaminergic systems in mediating cocaine's effects has been demonstrated through both pharmacological and genetic methods. Finally, and most importantly, unbiased genetic screens, feasible because of the simplicity and scale with which flies can be manipulated in the laboratory, have identified several novel genes and pathways whose role in cocaine behaviors had not been anticipated. Many of these genes and pathways have been validated in mammalian models of drug addiction. We focus in this review on the role of LIM-only proteins in cocaine-induced behaviors. copyright 2008 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Review Journal Name Neuropharmacology Volume 56 Issue Part SUPPL. 1 Page 97-106 Year of Publication 2009 Date of Publication 2009 COCAINE 2009 <195> Database EMBASE Accession Number 2009000494 Authors Stalnaker T.A. Takahashi Y. Roesch M.R. Schoenbaum G. Institution (Stalnaker, Takahashi, Roesch, Schoenbaum) Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, HSF-2 Room S251, Baltimore, MD 21201, United States. (Schoenbaum) Department of Psychiatry, University of Maryland School of Medicine, 20 Penn Street, HSF-2 Room S251, Baltimore, MD 21201, United States. (Schoenbaum) Department of Psychology, University of Maryland Baltimore County, Baltimore, MD 21228, United States. Country of Publication United Kingdom Title Neural substrates of cognitive inflexibility after chronic cocaine exposure. Source Neuropharmacology. 56(SUPPL. 1)(pp 63-72), 2009. Date of Publication: 2009. Publisher Elsevier Ltd Abstract Cognitive changes in addicts and animals exposed to addictive drugs have been extensively investigated over the past decades. One advantage of studying addiction using cognitive paradigms is that neural processing in addicts or drug-exposed animals can be compared to that in normal subjects. Tests of cognitive flexibility that measure the ability to change responding to a previously rewarded or punished stimulus are of potential interest in the study of addiction, because addiction can itself be viewed as an inability to change responding to stimuli previously associated with drug reward. One such test is reversal learning, which is impaired in cocaine addicts and animals that have chronically self-administered or been exposed to cocaine. A circuit including orbitofrontal cortex, basolateral amygdala and striatum subserves reversal learning. In rats that have been previously exposed to cocaine, neurons in these regions show selective and distinct changes in how they encode information during reversal learning. These changes suggest that in these rats, orbitofrontal cortex loses the ability to signal expected outcomes, and basolateral amygdala becomes inflexible in its encoding of cue significance. These changes could explain cocaine-induced impairments to cognitive flexibility and may have theoretical importance in addiction. copyright 2008 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Review Journal Name Neuropharmacology Volume 56 Issue Part SUPPL. 1 Page 63-72 Year of Publication 2009 Date of Publication 2009 COCAINE 2009 <230> Database EMBASE Accession Number 2009022224 Authors Oleson E.B. Roberts D.C.S. Institution (Oleson, Roberts) Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston-Salem, NC, United States. (Roberts) Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, United States. Country of Publication United Kingdom Title Behavioral economic assessment of price and cocaine consumption following selfadministration histories that produce escalation of either final ratios or intake. Source Neuropsychopharmacology. 34(3)(pp 796-804), 2009. Date of Publication: February 2009. Publisher Nature Publishing Group Abstract Various self-administration procedures are being developed to model specific aspects of the addiction process. For example, 'increased cocaine intake over time' has been modeled by providing long access (LgA) to cocaine during daily self-administration sessions under a fixedratio (FR1) reinforcement schedule. In addition, 'increased time and energy devoted to acquire cocaine' has been modeled by providing access to cocaine during daily selfadministration sessions under a progressive-ratio (PR) schedule. To investigate the distinctiveness of these models, the behavioral economics variables of consumption and price were applied to cocaine self-administration data. To assess changes in consumption and price, cocaine self-administration was tested across a descending series of doses (0.2370.001 mg per injection) under an FR1 reinforcement schedule to measure drug intake in the high dose range and thresholds in the low range. Cocaine consumption remained relatively stable across doses until a threshold was reached, at which maximal responding was observed. It was found that a history of LgA training produced an increase in cocaine consumption; whereas a history of PR training produced an increase in the maximal price (Pmax) expended for cocaine. Importantly, the concepts of consumption and price were found to be dissociable. That is, LgA training produced an increase in consumption but a decrease in Pmax, whereas PR training produced an increase in Pmax without increasing consumption. These results suggest that distinct aspects of the addiction process can be parsed using selfadministration models, thereby facilitating the investigation of specific neurobiological adaptations that occur through the addiction process. copyright 2009 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 34 Issue Part 3 Page 796-804 Year of Publication 2009 Date of Publication February 2009 COCAINE (A) 2009 <334> Database EMBASE Accession Number 2009300997 Authors Boudreau A.C. Ferrario C.R. Glucksman M.J. Wolf M.E. Institution (Wolf) Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064-3095, United States. (Boudreau, Ferrario, Wolf) Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States. (Glucksman) Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States. Country of Publication United Kingdom Title Signaling pathway adaptations and novel protein kinase A substrates related to behavioral sensitization to cocaine. Source Journal of Neurochemistry. 110(1)(pp 363-377), 2009. Date of Publication: July 2009. Publisher Blackwell Publishing Ltd Abstract Behavioral sensitization is an animal model for aspects of cocaine addiction. Cocainesensitized rats exhibit increased AMPA receptor (AMPAR) surface expression in the nucleus accumbens (NAc) which may in turn enhance drug seeking. To identify signaling pathways contributing to AMPAR up-regulation, we measured AMPAR surface expression and signaling pathway activation in the NAc of cocaine-sensitized rats, cocaine-exposed rats that failed to sensitize and saline controls on withdrawal days (WD) 1, 7, and 21. We focused on calcium/calmodulin-dependent protein kinase II (CaMKII), extracellular signal-regulated protein kinase (ERK), and protein kinase A (PKA). In sensitized rats, AMPAR surface expression was elevated on WD7 and WD21 but not WD1. ERK2 activation followed a parallel time-course, suggesting a role in AMPAR up-regulation. Both sensitized and nonsensitized rats exhibited CaMKII activation on WD7, suggesting that CaMKII activation is not sufficient for AMPAR up-regulation. PKA phosphorylation, measured using an antibody recognizing phosphorylated PKA substrates, increased gradually over withdrawal in sensitized rats, from below control levels on WD1 to significantly greater than controls on WD21. Using proteomics, novel sensitization-related PKA substrates were identified, including two structural proteins (CRMP-2 and alpha-tubulin) that we speculate may link PKA signaling to previously reported dendritic remodeling in NAc neurons of cocaine-sensitized rats. copyright 2009 International Society for Neurochemistry. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 110 Issue Part 1 Page 363-377 Year of Publication 2009 Date of Publication July 2009 COCAINE / AMPHETAMINES 2009 <347> Database EMBASE Accession Number 2009309721 Authors Zahniser N.R. Sorkin A. Institution (Zahniser, Sorkin) Department of Pharmacology, University of Colorado Denver, 12800 E. 19th Avenue, Aurora, CO 80045, United States. Country of Publication United Kingdom Title Trafficking of dopamine transporters in psychostimulant actions. Source Seminars in Cell and Developmental Biology. 20(4)(pp 411-417), 2009. Date of Publication: June 2009. Publisher Academic Press Abstract Brain dopamine (DA) plays a pivotal role in drug addiction. Since the plasma membrane DA transporter (DAT) is critical for terminating DA neurotransmission, it is important to understand how DATs are regulated and this regulation impacts drug addiction. The number of cell surface DATs is controlled by constitutive and regulated endocytic trafficking. Psychostimulants impact this trafficking. Amphetamines, DAT substrates, cause rapid upregulation and slower down-regulation of DAT whereas cocaine, a DAT inhibitor, increases surface DATs. Recent reports have begun to elucidate the molecular mechanisms of these psychostimulant effects and link changes in DAT trafficking to psychostimulant-induced reward/reinforcement in animal models. copyright 2009. ISSN 1084-9521 Publication Type Journal: Review Journal Name Seminars in Cell and Developmental Biology Volume 20 Issue Part 4 Page 411-417 Year of Publication 2009 Date of Publication June 2009 COCAINE 2009 <350> Database EMBASE Accession Number 2009270441 Authors del Castillo C. Morales L. Alguacil L.F. Salas E. Garrido E. Alonso E. Perez-Garcia C. Institution (del Castillo, Morales, Alguacil, Salas, Garrido, Alonso, Perez-Garcia) Department of Pharmacology, Technology and Pharmaceutical Development, University CEU San Pablo, Spain. Country of Publication United Kingdom Title Proteomic analysis of the nucleus accumbens of rats with different vulnerability to cocaine addiction. Source Neuropharmacology. 57(1)(pp 41-48), 2009. Date of Publication: July 2009. Publisher Elsevier Ltd Abstract Vulnerability to the addictive effects of drugs of abuse varies among individuals, but the biological basis of these differences are poorly known. This work tries to increase this knowledge by comparing the brain proteome of animals with different rate of extinction of cocaine-seeking behaviour. To achieve this goal, we used a place-preference paradigm to separate Sprague Dawley rats in two groups: rats that extinguished (E) and rats that did not extinguish (NE) cocaine-seeking behaviour after a five-day period of drug abstinence. Once the phenotype was established, we compared the protein expression in the nucleus accumbens (NAC) of these animals after a single injection of either saline (SAL) or cocaine (COC, 15 mg/kg). The analysis of protein expression was performed by 2-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time of flight mass spectrometry. When comparing E SAL and NE SAL animals we found significant differences in the expression level of 5 proteins: ATP synthase subunit alpha, fumarate hydratase, transketolase, NADH dehydrogenase [ubiquinone] flavoprotein 2 and glutathione transferase omega-1. A single injection of COC differently alters the NAC proteome of E and NE rats; thus in E COC animals there was an alteration in the expression of 6 proteins, including dihydropyrimidinase-related protein 2 and NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10; whereas in NE COC rats 9 proteins were altered (including alphasynuclein, peroxiredoxin-2 and peroxiredoxin-5). These proteins could be potential biomarkers of individual vulnerability to cocaine abuse and may be helpful in designing new treatments for cocaine addiction. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Article Journal Name Neuropharmacology Volume 57 Issue Part 1 Page 41-48 Year of Publication 2009 Date of Publication July 2009 COCAINE 2009 <394> Database EMBASE Accession Number 2009319826 Authors Kelamangalath L. Wagner J.J. Institution (Kelamangalath, Wagner) Department of Physiology and Pharmacology, University of Georgia, 501 D.W. Brooks Drive, Athens, GA 30602-7389, United States. (Kelamangalath, Wagner) Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, United States. (Wagner) Neuroscience Program, University of Georgia, Athens, GA, United States. Country of Publication United Kingdom Title Effects of abstinence or extinction on cocaine seeking as a function of withdrawal duration. Source Behavioural Pharmacology. 20(2)(pp 195-203), 2009. Date of Publication: March 2009. Publisher Lippincott Williams and Wilkins Abstract The resumption of drug-seeking behavior after abstinence or extinction is commonly studied model for relapse in addiction. For the benefits of extinction training over a given withdrawal period to be determined, it is necessary to discriminate between the potentially overlapping occurrence of incubation with that of spontaneous recovery. This comparison has been assessed using a between-subjects design in groups of abstinent and extinguished rats tested at various withdrawal periods after cocaine self-administration. Multiple forms of priming were used to evoke the resumption of drug seeking, as different priming stimuli have been reported to use distinct neurobiological mechanisms and therefore may exhibit different temporal characteristics. In abstinent animals (30 days), neither the noncontingent conditioned stimuli-primed nor the noncontingent cocaine-primed drug seeking displayed incubation, whereas the drug seeking provoked by exposure to the contextual cues of the operant chamber significantly increased. In extinguished animals, evidence of spontaneous recovery of responding was observed after priming with exposure to either contextual or cocaine-priming stimuli. Finally, extinction training remained effective in reducing the reinstatement response levels after contextual or cocaine priming even if such training was initiated after an extended period (24 days) of abstinence. These findings provide further insight into the time-dependent effects of abstinence and extinction on the resumption of drug-seeking behavior. copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. ISSN 0955-8810 Publication Type Journal: Article Journal Name Behavioural Pharmacology Volume 20 Issue Part 2 Page 195-203 Year of Publication 2009 Date of Publication March 2009 COCAINE 2009 <418> Database EMBASE Accession Number 2009357878 Authors Fox H.C. Jackson E.D. Sinha R. Institution (Fox, Jackson, Sinha) Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, 2 Church St. South, Suite 209, Room 209Q, New Haven, CT 06519, United States. Country of Publication United Kingdom Title Elevated cortisol and learning and memory deficits in cocaine dependent individuals: Relationship to relapse outcomes. Source Psychoneuroendocrinology. 34(8)(pp 1198-1207), 2009. Date of Publication: September 2009. Publisher Elsevier Ltd Abstract Objective: Cocaine dependence is characterized by stress system dysregulation, including elevated cortisol activity, emotional negativity, and behavioral disinhibition. High levels of stress and glucocorticoids are also known to affect learning, memory and executive function. Therefore, we examined the relationships between chronic cocaine use, elevated distress and learning and memory dysfunction in abstinent cocaine dependent (CD) individuals, and whether these measures were associated with cocaine relapse outcomes. Method: Stress was assessed in 36 inpatient treatment engaged CD individuals and 36 demographically matched healthy control (HC) participants using the Perceived Stress Scale (PSS) and repeated morning salivary cortisol levels over three consecutive days. The Rey Auditory Verbal Learning Test (RAVLT) was conducted to measure verbal learning, memory, and executive function. Prospective assessment of cocaine use outcomes during 90 days following discharge from inpatient treatment was also conducted. Results: CD patients showed higher levels of distress compared to controls in PSS scores and cortisol levels. They also demonstrated a significantly reduced learning curve, and fewer correct responses and more errors on recognition. Elevated cortisol was significantly associated with worse RAVLT performance in CD patients. Poor memory scores, but not distress measures, were significantly associated with greater cocaine use after inpatient treatment. Conclusions: These findings are the first to demonstrate that learning and memory deficits in CD individuals are associated with enhanced cortisol and with cocaine use outcomes after inpatient treatment. The findings are consistent with recent addiction models suggesting that chronic cocainerelated neuroadaptations affects learning and memory function, which in turn, influences drug use outcomes. copyright 2009 Elsevier Ltd. All rights reserved. ISSN 0306-4530 Publication Type Journal: Article Journal Name Psychoneuroendocrinology Volume 34 Issue Part 8 Page 1198-1207 Year of Publication 2009 Date of Publication September 2009 COCAINE 2009 <436> Database EMBASE Accession Number 2009412452 Authors Defulio A. Donlin W.D. Wong C.J. Silverman K. Institution (Defulio, Donlin, Wong, Silverman) Department of Psychiatry and Behavioral Sciences, 5200 Eastern Avenue, Baltimore, MD 21224, United States. Country of Publication United Kingdom Title Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: A randomized controlled trial. Source Addiction. 104(9)(pp 1530-1538), 2009. Date of Publication: September 2009. Publisher Blackwell Publishing Ltd Abstract Context Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective To determine whether employment-based abstinence reinforcement can be an effective longterm maintenance intervention for cocaine dependence. Design Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. Setting A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. Intervention Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main outcome measure Cocaine-negative urine samples at monthly assessments across 1 year of employment. Results During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60-8.69]. Conclusions Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments for drug dependence. Work-places could serve as therapeutic agents in the treatment of drug dependence by arranging longterm employment-based contingency management programs. copyright 2009 Society for the Study of Addiction. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 104 Issue Part 9 Page 1530-1538 Year of Publication 2009 Date of Publication September 2009 COCAINE (A) 2009 <484> Database EMBASE Accession Number 2009412433 Authors Smith R.J. See R.E. Aston-Jones G. Institution (Smith, See, Aston-Jones) Department of Neurosciences, Medical University of South Carolina, 403 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425-5100, United States. Country of Publication United Kingdom Title Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaineseeking. Source European Journal of Neuroscience. 30(3)(pp 493-503), 2009. Date of Publication: August 2009. Publisher Blackwell Publishing Ltd Abstract The orexin/hypocretin system has recently been implicated in reward-processing and addiction. We examined the involvement of the orexin system in cue-induced reinstatement of extinguished cocaine-seeking by administering the orexin 1 receptor antagonist SB-334867 (SB) or the orexin 2 receptor antagonist 4-pyridylmethyl (S)-tert-leucyl 6,7-dimethoxy-1,2,3,4tetrahydroisoquinoline (4PT) prior to reinstatement testing. Male Sprague Dawley rats selfadministered cocaine in 2-h sessions for 10 days, followed by extinction training. Reinstatement of cocaine-seeking was elicited by presentation of tone + light cues previously paired with cocaine infusions. SB (10, 20 and 30 mg/kg) dose-dependently decreased cueinduced reinstatement of cocaine-seeking without significantly affecting responding during late extinction. 4PT (10 and 30 mg/kg) did not significantly alter cue-induced reinstatement. In separate experiments, the highest doses of SB and 4PT had no significant effect on established cocaine self-administration, and 4PT reduced spontaneous activity in a locomotor test to a greater extent than SB. Finally, SB (30 mg/kg) had no effect on the acquisition of cocaine-paired cues during a Pavlovian cocaine-stimulus conditioning session in the operant chamber. Pretreatment with SB prior to the Pavlovian acquisition session had no effect on subsequent cue-induced reinstatement of cocaine-seeking elicited by those cues. However, pretreatment with SB prior to a second reinstatement session in the same animals significantly attenuated the expression of cue-induced reinstatement. These results show that orexin transmission at the orexin 1 receptor, but not the orexin 2 receptor, is necessary for the reinstatement of cocaine-seeking elicited by drug-paired cues and that orexin signaling is not critical for cocaine reinforcement or cocaine-stimulus conditioning. copyright Federation of European Neuroscience Societies and Blackwell Publishing Ltd. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 30 Issue Part 3 Page 493-503 Year of Publication 2009 Date of Publication August 2009 COCAINE (A) 2009 <490> Database EMBASE Accession Number 2009418829 Authors Opris I. Hampson R.E. Deadwyler S.A. Institution (Opris, Hampson, Deadwyler) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, United States. Country of Publication United Kingdom Title The encoding of cocaine vs. natural rewards in the striatum of nonhuman primates: categories with different activations. Source Neuroscience. 163(1)(pp 40-54), 2009. Date of Publication: 29 Sep 2009. Publisher Elsevier Ltd Abstract The behavioral and motivational changes that result from use of abused substances depend upon activation of neuronal populations in the reward centers of the brain, located primarily in the corpus striatum in primates. To gain insight into the cellular mechanisms through which abused drugs reinforce behavior in the primate brain, changes in firing of neurons in the ventral (VStr, nucleus accumbens) and dorsal (DStr, caudate-putamen) striatum to "natural" (juice) vs. drug (i.v. cocaine) rewards were examined in four rhesus monkeys performing a visual Go-Nogo decision task. Task-related striatal neurons increased firing to one or more of the specific events that occurred within a trial represented by (1) Target stimuli (Go trials) or (2) Nogotarget stimuli (Nogo trials), and (3) Reward delivery for correct performance. These three cell populations were further subdivided into categories that reflected firing exclusively on one or the other type of signaled reward (juice or cocaine) trial (20%-30% of all cells), or, a second subpopulation that fired on both (cocaine and juice) types of rewarded trial (50%). Results show that neurons in the primate striatum encoded cocaine-rewarded trials similar to juice-rewarded trials, except for (1) increased firing on cocaine-rewarded trials, (2) prolonged activation during delivery of i.v. cocaine infusion, and (3) differential firing in ventral (VStr cells) vs. dorsal (DStr cells) striatum cocaine-rewarded trials. Reciprocal activations of antithetic subpopulations of cells during different temporal intervals within the same trial suggest a functional interaction between processes that encode drug and natural rewards in the primate brain. copyright 2009 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 163 Issue Part 1 Page 40-54 Year of Publication 2009 Date of Publication 29 Sep 2009 COCAINE / AMPHETAMINES 2009 <491> Database EMBASE Accession Number 2009404849 Authors Borders T.F. Booth B.M. Falck R.S. Leukefeld C. Wang J. Carlson R.G. Institution (Borders) Department of Health Policy and Management, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, United States. (Booth) Division of Health Services Research, Department of Psychiatry, University of Arkansas for Medical Sciences, United States. (Booth) VA Health Services Research and Development, Center for Mental Health and Outcomes Research, Central Arkansas Veterans Healthcare System, United States. (Falck, Wang, Carlson) Center for Interventions, Treatment, and Addictions Research, Boonshoft School of Medicine, Wright State University, United States. (Leukefeld) Department of Behavioral Science, College of Medicine, University of Kentucky, United States. Country of Publication United Kingdom Title Longitudinal changes in drug use severity and physical health-related quality of life among untreated stimulant users. Source Addictive Behaviors. 34(11)(pp 959-964), 2009. Date of Publication: November 2009. Publisher Elsevier Ltd Abstract The primary objective of this study was to investigate whether drug use severity is associated with physical health-related quality of life (HRQL) over time. Data are from a longitudinal, multi-state, natural history community study of users of cocaine and/or methamphetamine who were interviewed at 6-month intervals over 2 years with a 79% followup participation rate. Physical HRQL was assessed with the physical component summary (PCS) of the SF-8[trademark] Health Survey and drug, alcohol, and psychiatric severity were all assessed with the Addiction Severity Index (ASI). Random coefficient regression analyses were conducted to test for longitudinal associations between the independent variables and SF-8 PCS scores. Reductions in drug use severity over time were accompanied by only minor improvements in SF-8 PCS scores, underscoring the potential long-term harm of illicit drug use on physical health. Greater psychiatric severity was strongly associated with lower SF-8 PCS scores, suggesting that clinical attention to mental health issues could potentially lead to improvements in perceived physical health as well as among stimulant users. copyright 2009 Elsevier Ltd. ISSN 0306-4603 Publication Type Journal: Article Journal Name Addictive Behaviors Volume 34 Issue Part 11 Page 959-964 Year of Publication 2009 Date of Publication November 2009 COCAINE 2009 <517> Database EMBASE Accession Number 2009459228 Authors Kim W.Y. Shin S.R. Kim S. Jeon S. Kim J.-H. Institution (Kim, Shin, Kim, Kim) Department of Physiology, Brain Korea 21 Project for Medical Science, Brain Research Institute, 250 Seongsanno, Seodaemungu, Seoul 120-752, South Korea. (Jeon) Medical Science Research Center, Institute of Biotechnology, Dongguk University Research, 814 Siksadong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea. Country of Publication United Kingdom Title Cocaine regulates ezrin-radixin-moesin proteins and RhoA signaling in the nucleus accumbens. Source Neuroscience. 163(2)(pp 501-505), 2009. Date of Publication: 06 Oct 2009. Publisher Elsevier Ltd Abstract The ezrin-radixin-moesin (ERM) proteins are a family of widely distributed membraneassociated proteins and have been implicated not only in cell-shape determination but also in signaling pathway. The nucleus accumbens (NAcc) is an important neuronal substrate mediating the effects of drugs of abuse. However, it has not been determined yet how ERM proteins are regulated in this site by drugs of abuse. Here we show in rat that the phosphorylation levels of ERM protein are dose- and time-dependently decreased in the NAcc by a single injection of cocaine (15 or 30 mg/kg i.p.). Further, we show that the amount of active RhoA, a small GTPase protein, is significantly reduced in the NAcc by cocaine, while the phosphorylation levels of ERM protein are also decreased by bilateral microinjections in this site of the Rho kinase inhibitors. Together, these results suggest that cocaine reduces phosphorylated ERM levels in the NAcc by making downregulation of RhoA-Rho kinase signaling, which may importantly contribute to initiate synaptic changes in this site leading to drug addiction. copyright 2009 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 163 Issue Part 2 Page 501-505 Year of Publication 2009 Date of Publication 06 Oct 2009 COCAINE 2009 <524> Database EMBASE Accession Number 2009472914 Authors Lyness J.R. Institution (Lyness) State Pathologist's Department, Institute of Forensic Medicine, The Queen's University of Belfast, Belfast BT12 6BS, United Kingdom. Country of Publication United Kingdom Title Cocaine: Recent trends in Northern Ireland. Source Ulster Medical Journal. 78(2)(pp 94-98), 2009. Date of Publication: May 2009. Publisher Ulster Medical Society Abstract A review of autopsy reports in cases in which cocaine featured in the cause of death in Northern Ireland revealed that there were 18 deaths between 1st January 1999 and 31st December 2007. Analysis revealed an increasing incidence of these deaths during the study period and this is compared to national statistics and those published by local drug addiction services and police. copyright The Ulster Medical Society, 2009. ISSN 0041-6193 Publication Type Journal: Review Journal Name Ulster Medical Journal Volume 78 Issue Part 2 Page 94-98 Year of Publication 2009 Date of Publication May 2009 ECSTASY / COCAINE (A) 2009 <528> Database EMBASE Accession Number 2009481220 Authors Daza-Losada M. Rodriguez-Arias M. Aguilar M.A. Minarro J. Institution (Daza-Losada, Rodriguez-Arias, Aguilar, Minarro) Unidad de Investigacion Psicobiologia de Las Drogodependencias, Departamento de Psicobiologia, Universitat de Valencia, Avda. Blasco Ibanez 21, 46010, Valencia, Spain. Country of Publication United Kingdom Title Acquisition and reinstatement of MDMA-induced conditioned place preference in mice pre-treated with MDMA or cocaine during adolescence: PRECLINICAL STUDY. Source Addiction Biology. 14(4)(pp 447-456), 2009. Date of Publication: October 2009. Publisher Blackwell Publishing Ltd Abstract Those who take ecstasy are more likely to consume other drugs than non-users with cocaine abuse being reported by 75.5% of high school student MDMA (+/- 3,4methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to evaluate the effects of exposure during adolescence to MDMA, cocaine or to both drugs on the MDMAinduced conditioned place preference (CPP) in adult mice. Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to 30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was initiated (PD52). Acquisition of CPP was induced with a sub-threshold dose of MDMA (1.25 mg/kg) only in animals treated during adolescence with MDMA alone. Preference was established in all the groups after conditioning with 10 mg/kg of MDMA, while the time required to achieve extinction was longer in those pre-treated with cocaine or MDMA alone (46 and 28 sessions, respectively). Moreover, preference was reinstated with progressively lower priming doses of MDMA in mice pre-treated with MDMA or cocaine alone. These results demonstrate that early exposure to MDMA or cocaine induces long-lasting changes that last until adulthood and modify the response of animals to MDMA. copyright 2009 Society for the Study of Addiction. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 14 Issue Part 4 Page 447-456 Year of Publication 2009 Date of Publication October 2009 COCAINE 2009 <538> Database EMBASE Accession Number 2009481210 Authors Pentkowski N.S. Acosta J.I. Browning J.R. Hamilton E.C. Neisewander J.L. Institution (Pentkowski, Acosta, Browning, Hamilton, Neisewander) Department of Psychology, Arizona State University, P.O. Box 871104, Tempe, AZ 85287, United States. Country of Publication United Kingdom Title Stimulation of 5-HT1B receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior: PRECLINICAL STUDY. Source Addiction Biology. 14(4)(pp 419-430), 2009. Date of Publication: October 2009. Publisher Blackwell Publishing Ltd Abstract Paradoxically, stimulation of 5-HT1B receptors (5-HT 1BRs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT1BR agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the selfadministration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaineseeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT1BRs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT1BRs may be a novel target for developing medications for cocaine dependence. copyright 2009 Society for the Study of Addiction. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 14 Issue Part 4 Page 419-430 Year of Publication 2009 Date of Publication October 2009 COCAINE (A) 2009 <590> Database EMBASE Accession Number 2009496555 Authors Neumaier J.F. McDevitt R.A. Polis I.Y. Parsons L.H. Institution (Neumaier, McDevitt) Box 359911, Harborview Medical Center, University of Washington, 325 9th Ave, Seattle, WA 98104, United States. (McDevitt) Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA, United States. (Polis, Parsons) Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, San Diego, CA, United States. Country of Publication United Kingdom Title Acquisition of and withdrawal from cocaine self-administration regulates 5-HT1B mRNA expression in rat striatum. Source Journal of Neurochemistry. 111(1)(pp 217-227), 2009. Date of Publication: October 2009. Publisher Blackwell Publishing Ltd Abstract This study investigated how different stages of cocaine self-administration in rats affect the expression of two serotonin receptors in dorsal and ventral striatum, the 5-HT1B and 5-HT6 subtypes, which have both been implicated in mediating some aspects of cocaine-related behaviors. In the first experiment, rats were trained to work for saccharin (oral) or cocaine (i.v.) reinforcers. We found that continuous access to cocaine for 23 days did not change the level of 5-HT1B mRNA expression compared to control animals receiving saccharin. However, a single cocaine session, given either by self-administration or non-contingently, increased 5-HT1B mRNA in dorsal striatum, whereas forced abstinence for two weeks after cocaine reduced 5-HT1B mRNA expression in the same subregion. 5-HT6 mRNA was not changed by any of these treatments. A follow-up experiment investigated the effects of limited versus extended access to cocaine as well as forced abstinence, and we found that 14 days of forced abstinence significantly reduced 5-HT1B mRNA throughout the dorsal and ventral striatum compared to no withdrawal. These results suggest that the influence of 5-HT1B receptors in striatal projection neurons may be increased during cocaine acquisition and reduced after forced abstinence and may therefore be targets for pharmacological intervention in addiction. copyright 2009 International Society for Neurochemistry. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 111 Issue Part 1 Page 217-227 Year of Publication 2009 Date of Publication October 2009 COCAINE 2009 <599> Database EMBASE Accession Number 2009465616 Authors Fuchs R.A. Bell G.H. Ramirez D.R. Eaddy J.L. Su Z.-I. Institution (Fuchs, Bell, Ramirez, Eaddy, Su) Department of Psychology, University of North Carolina, Davie Hall, CB#3270, Chapel Hill, NC, United States. Country of Publication United Kingdom Title Basolateral amygdala involvement in memory reconsolidation processes that facilitate drug context-induced cocaine seeking. Source European Journal of Neuroscience. 30(5)(pp 889-900), 2009. Date of Publication: September 2009. Publisher Blackwell Publishing Ltd Abstract Understanding the neurobiological underpinnings of putative memory stabilization processes that maintain context-response-cocaine associations in long-term memory and underlie contextual control over addictive behavior is of great interest from an addiction treatment perspective. Using an instrumental animal model of contextual drug relapse we show that the protein synthesis inhibitor anisomycin, administered into the basolateral amygdala (BLA) immediately after limited (15- or 60-min) re-exposure to a previously cocaine-paired context, subsequently disrupted the ability of the previously cocaine-paired context to reinstate extinguished cocaine-seeking behavior relative to vehicle. Consistent with a BLA-mediated memory reconsolidation deficit, a similar impairment in cocaine-seeking behavior was not observed in (i) 'no-reactivation' control groups that received anisomycin into the BLA after (re)exposure to either a novel unpaired or an extinction-paired context or in (ii) a neuroanatomical control group that received anisomycin into the posterior caudate-putamen, dorsally adjacent to the BLA, after re-exposure to the cocaine-paired context. Furthermore, anisomycin administered into the BLA after brief (5-min) or extensive (120-min) re-exposure to the cocaine-paired context (which was sufficient to extinguish cocaine-seeking behavior in a vehicle control group) also failed to alter responding. Together, these findings suggest that re-exposure to a cocaine-paired context in the absence of cocaine reinforcement is sufficient to trigger memory reconsolidation processes that support future drug-seeking behavior. The presence and duration of drug-related memory reactivation critically influences, and anisomycin-sensitive mechanisms in the BLA selectively control, this phenomenon. These findings support the feasibility of novel pharmacotherapeutic approaches that selectively inhibit the reconsolidation of cocaine-related memories in order to prevent drug relapse. copyright 2009 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 30 Issue Part 5 Page 889-900 Year of Publication 2009 Date of Publication September 2009