There are currently no FDA-approved medications for cocaine addiction. In the previous funding period, several animal models of cocaine abuse were used by this Center to investigate the neuropharmacology of chronic cocaine exposure. The studies described in Project 1 combine three research areas that were separated into distinct Projects in the previous version of the Center (formerly Projects 3, 5 and 6). These studies are designed to systematically investigate in monkeys and rats current medications used clinically to beat cocaine addiction, as well as drugs in the clinical "pipeline" and drugs that are not approved for human use, but could provide information related to mechanisms of action related to clinical efficacy.
Specific Aim 1 will use rhesus monkeys self-administering cocaine to examine the effects of chronic administration of drugs. Treatment drugs that selective decrease cocaine- relative to food-reinforced responding, with no evidence of tolerance or attenuation by higher cocaine doses, will be evaluated in monkey models of cognition (Specific Aim 2). A positive outcome in models of cognition (i.e., improvement in performance) will yield additional studies in experimentally naive monkeys in combination with imaging studies (Projects 2 and 3). Finally, Specific Aim 3 will examine the effects of acute and chronic administration of drug treatments in several rat models of cocaine self-administration. When complete, the studies in this Project will provide basic science information in monkeys and rats across several behavioral endpoints in which different aspects of addiction are modeled, which should be of relevance to clinicians.

Public Health Relevance

By combining a top-down approach, using drugs currently being evaluated clinically, with a mechanistic approach in several animal models of self-administration and cognition, areas of convergence will be identified that are relevant to identifying neuropharmacological mechanisms for effective treatment agents for cocaine addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA006634-22
Application #
8471086
Study Section
Special Emphasis Panel (ZDA1-EXL-T)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
22
Fiscal Year
2013
Total Cost
$482,707
Indirect Cost
$184,837
Name
Wake Forest University Health Sciences
Department
Type
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Fetterhoff, Dustin; Opris, Ioan; Simpson, Sean L et al. (2015) Multifractal analysis of information processing in hippocampal neural ensembles during working memory under ??-tetrahydrocannabinol administration. J Neurosci Methods 244:136-53
Siciliano, Cody A; Calipari, Erin S; Ferris, Mark J et al. (2014) Biphasic mechanisms of amphetamine action at the dopamine terminal. J Neurosci 34:5575-82
Smith, Hilary R; Beveridge, Thomas J R; Nader, Michael A et al. (2014) Regionally-specific alterations in myelin proteins in nonhuman primate white matter following prolonged cocaine self-administration. Drug Alcohol Depend 137:143-7
Pattison, Lindsey P; McIntosh, Scot; Sexton, Tammy et al. (2014) Changes in dopamine transporter binding in nucleus accumbens following chronic self-administration cocaine: heroin combinations. Synapse 68:437-44
Siciliano, Cody A; Calipari, Erin S; Jones, Sara R (2014) Amphetamine potency varies with dopamine uptake rate across striatal subregions. J Neurochem 131:348-55
Beveridge, Thomas J R; Smith, Hilary R; Nader, Susan H et al. (2014) Functional consequences of cocaine re-exposure after discontinuation of cocaine availability. Neuropharmacology 85:528-37
Ferris, Mark J; EspaƱa, Rodrigo A; Locke, Jason L et al. (2014) Dopamine transporters govern diurnal variation in extracellular dopamine tone. Proc Natl Acad Sci U S A 111:E2751-9
Gill, Kathryn E; Chappell, Ann M; Beveridge, Thomas J R et al. (2014) Chronic methylphenidate treatment during early life is associated with greater ethanol intake in socially isolated rats. Alcohol Clin Exp Res 38:2260-8
Nader, Michael A; Banks, Matthew L (2014) Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging. Neuropharmacology 76 Pt B:510-7
Bough, Kristopher J; Amur, Shashi; Lao, Guifang et al. (2014) Biomarkers for the development of new medications for cocaine dependence. Neuropsychopharmacology 39:202-19

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