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.
