The long-term objective of the proposed work is to gain an increased understanding of conditioned drug effects. The significance of the work lies in the important role played by learning factors in drug abuse phenomena such as tolerance, drug craving and relapse. The work utilizes 6-hydroxydopamine lesioned rodent preparations. The primary preparation, the unilaterally nigral lesioned rat, is a well characterized model of proven utility in the study of dopamine (DA) function. In this preparation direct and indirect DA agonists result in oppositely directed rotational (circling) behavior. A clear and quantifiable conditioned drug-like effect can be demonstrated in this preparation after a single administration of a direct-acting DA agonist. An analogous conditioned drug effect has not been demonstrated utilizing indirect-acting DA agonists. The objective of the experiments presented here is to further characterize this extraordinary conditioned behavior and investigate its potential for analyzing mechanisms involved in conditioning.
The specific aims of the proposed experiments ar to determine the pharmacological and temporal requirements for conditioned rotation in unilaterally lesioned rats as well as the effect of varying the route of drug administration. The generality of what appears to be a profound, fundamental advantage to conditioning in the denervated striatum will be tested in another species (mouse) and in a different rat preparation (whole brain DA depleted). A preliminary determination of the utility of apomorphine-conditioned rotation in investigation of drug stimulus effects and drug-drug, drug-environment interactions will be made by pairing apomorphine administration with drugs which do not have DA agonist effects.
