The dopamine D2 and D3 receptors are differentially expressed at high levels within the mesolimbic dopaminergic system and the nucleus accumbens, areas known to be important in the regulation of the reinforcing properties of drugs of abuse. It is hypothesized that the dopamine D2 and D3 receptors are differentially involved in reward and reinforcement, and that utilization of selective D2 and D3 agonists and antagonists will allow for a more accurate assessment of the in vivo roles of the D2 and D3 receptors. Assignment of roles for D2 and D3 has been complicated by the fact that there are currently no purely D2 or D3 selective agonists or antagonists, rather existing compounds have varying degrees of selectivity for D2 and D3.
The specific aims to be tested are: (1) in vivo characterization of existing and novel dopaminergic agonist and antagonist with regard to their selectivity for, and activities at the D2 and D3 receptors in rhesus monkeys and rats, (2) investigation of the reinforcing properties of D2 and D3 acting agonists and antagonists, and (3) evaluation of D2 and D3 agonists and antagonists with regard to their ability to modulate reinforcement maintained by psychostimulants such as cocaine. Taken together, the results of these experiments will allow for a better understanding of the specific roles of the D2 and D3 receptors in the reward and reinforcement pathways of the brain as well as provide valuable information towards the development of novel compounds as well as therapeutics aimed at drug abuse and addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA019322-02
Application #
7127312
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lawrence, Diane M
Project Start
2005-09-05
Project End
2008-09-04
Budget Start
2006-09-05
Budget End
2007-09-04
Support Year
2
Fiscal Year
2006
Total Cost
$32,686
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Collins, Gregory T; Truong, Yen Nhu-Thi; Levant, Beth et al. (2011) Behavioral sensitization to cocaine in rats: evidence for temporal differences in dopamine D3 and D2 receptor sensitivity. Psychopharmacology (Berl) 215:609-20
Collins, Gregory T; Woods, James H (2009) Influence of conditioned reinforcement on the response-maintaining effects of quinpirole in rats. Behav Pharmacol 20:492-504
Collins, Gregory T; Woods, James H (2007) Drug and reinforcement history as determinants of the response-maintaining effects of quinpirole in the rat. J Pharmacol Exp Ther 323:599-605
Collins, Gregory T; Newman, Amy Hauck; Grundt, Peter et al. (2007) Yawning and hypothermia in rats: effects of dopamine D3 and D2 agonists and antagonists. Psychopharmacology (Berl) 193:159-70