This is a new application for a NIDA Senior Scientist Award (K05). The candidate is William L. Woolverton, Ph.D., Professor of Psychiatry and Pharmacology at the University of Mississippi Medical Center (UMC). He has a 30-year history of drug abuse research and has been funded continuously by NIDA for the past 18 years. His primary area of research is intravenous drug self-administration by non-human primates. This animal model has played a central role in the evolution of our understanding of drug taking. The PI proposes to extend this model using novel approaches to examine in detail neurobiological and behavioral mechanisms that control drug taking. The proposed research reflects current grant support from NIDA. Neurobiological aims focus on the role of pharmacodynamic and pharmacokinetic mechanisms that determine the reinforcing effects of drugs that act at monoamine transporters. In addition, we will examine the possibility that self-administration of these compounds is partially determined by aversive effects that involve monoamine transporters or other neurotransmitter systems. Behavioral aims revolve around the hypothesis that loss of normal mechanisms controlling choice contributes to loss of control of drug self-administration, a defining feature of drug abuse. Drug choice will be examined in the context of major theoretical models of choice, including matching, delay discounting, and behavioral economics. Overall, this research will extend and refine our knowledge of neurobiological and behavioral determinants of drug taking. In addition, it will have important implications for the development of treatment medications, and suggest behavioral approaches to modifying the choice to self-administer a drug. ? ? This K05 will ensure that the candidate can concentrate his effort on his career as a drug abuse scientist. Continued career development will come from a combination of new research projects and new questions from previous projects, as well as to new and continuing collaborations. This will be facilitated by the large and active neuroscience community at UMC. Trainees at both pre- and postdoctoral levels will participate in this research program. An important goal will be to provide them with the skills needed for a career of research on the neurobehavioral pharmacology of drug self-administration. In addition, the candidate will continue to participate in other professional activities that contribute to overall career development, such as teaching and active membership on journal editorial boards, government advisory committees, and scientific organizations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA015343-05
Application #
7117001
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lynch, Minda
Project Start
2002-09-01
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$121,500
Indirect Cost
Name
University of Mississippi Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Woolverton, W L; Wang, Zhixia; Vasterling, Theresa et al. (2008) Self-administration of drug mixtures by monkeys: combining drugs with comparable mechanisms of action. Psychopharmacology (Berl) 196:575-82
Woolverton, W L; Wang, Zhixia; Vasterling, Theresa et al. (2008) Self-administration of cocaine-remifentanil mixtures by monkeys: an isobolographic analysis. Psychopharmacology (Berl) 198:387-94
Wang, Zhixia; Woolverton, William L (2007) Self-administration of cocaine-antihistamine combinations: super-additive reinforcing effects. Eur J Pharmacol 557:159-60
Wang, Zhixia; Ordway, Gregory A; Woolverton, William (2007) Effects of cocaine on monoamine uptake as measured ex vivo. Neurosci Lett 413:191-5
Wang, Zhixia; Woolverton, William L (2007) Estimating the relative reinforcing strength of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine. Psychopharmacology (Berl) 189:483-8
Wee, Sunmee; Woolverton, William L (2006) Self-administration of mixtures of fenfluramine and amphetamine by rhesus monkeys. Pharmacol Biochem Behav 84:337-43
Wee, Sunmee; Carroll, F Ivy; Woolverton, William L (2006) A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants. Neuropsychopharmacology 31:351-62
Wee, Sunmee; Wang, Zhixia; He, Rong et al. (2006) Role of the increased noradrenergic neurotransmission in drug self-administration. Drug Alcohol Depend 82:151-7
Woolverton, William L; Anderson, Karen G (2006) Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys. Psychopharmacology (Berl) 186:99-106
Fantegrossi, W E; Winger, G; Woods, J H et al. (2005) Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys. Drug Alcohol Depend 77:161-8

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