The repeated administration of cocaine results in the development of behavioral sensitization, characterized by a progressive increase in both the motor-activating and rewarding effects of cocaine. This phenomenon has received a great deal of research attention because the neurochemical mechanisms mediating the development and persistence of behavioral sensitization are thought to play an important role in the development of stimulant-induced psychosis, as well as in the maintenance of compulsive drug-seeking behavior and relapse in recovering addicts. Despite this research attention, the exact mechanisms remain unknown. Research indicates that behavioral sensitization develops as a result of both associative (i.e., learning) and nonassociative (i.e., repeated drug exposure) processes. The major objective of the proposed project is to determine the involvement of specific dopaminergic receptor subtypes in both the associative and nonassociative components of behavioral sensitization to the locomotor-activating effects of cocaine. The first series of experiments will systematically determine the contribution of associative and nonassociative mechanisms to the development and persistence of cocaine-induced behavioral sensitization. Then, a series of experiments will be conducted to determine whether the development and/or persistence of associative and nonassociative behavioral sensitization to cocaine can be blocked by the concurrent administration of selective dopamine receptor subtype antagonists.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
5R15DA009687-05
Application #
2897963
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lynch, Minda
Project Start
1998-07-01
Project End
2001-06-30
Budget Start
1999-09-01
Budget End
2001-06-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Morehead State University
Department
Psychology
Type
Other Domestic Higher Education
DUNS #
041957010
City
Morehead
State
KY
Country
United States
Zip Code
40351
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Bardo, M T; Robinet, P M; Mattingly, B A et al. (2001) Effect of 6-hydroxydopamine or repeated amphetamine treatment on mesencephalic mRNA levels for AMPA glutamate receptor subunits in the rat. Neurosci Lett 302:133-6
Mattingly, B A; Rice, L L; Langfels, M et al. (2000) Repeated treatments with 7-OH-DPAT: context-independent behavioral sensitization and conditioned hyperactivity. Pharmacol Biochem Behav 65:241-6
Mattingly, B A; Himmler, C; Bonta, T et al. (1998) Effects of selective dopamine D1- and D2-type receptor antagonists on the development of behavioral sensitization to 7-OH-DPAT. Psychopharmacology (Berl) 140:387-97
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Mattingly, B A; Rowlett, J K; Ellison, T et al. (1996) Cocaine-induced behavioral sensitization: effects of haloperidol and SCH 23390 treatments. Pharmacol Biochem Behav 53:481-6
Mattingly, B A; Fields, S E; Langfels, M S et al. (1996) Repeated 7-OH-DPAT treatments: behavioral sensitization, dopamine synthesis and subsequent sensitivity to apomorphine and cocaine. Psychopharmacology (Berl) 125:33-42