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 investigates conditioning in 6-hydroxydopamine lesioned rodent preparations. In the primary preparation, the unilaterally nigral rat, direct and indirect dopamine (DA) agonists result in oppositely directed rotational (circling)behavior. A robust and quantifiable conditioned drug-like effect can be demonstrated in this preparation months after even a single administration of the prototypic direct-acting DA agonist, apomorphine. The conditioned rotation is ordinarily elicited by the external environment associated with drug administration, but it can be brought under discriminative control of other drugs. Thus, for example, neither pentobarbital nor ethanol ordinarily induce circling, but each can result in active rotation after its administration has been paired several times with a small dose of apomorphine. The proposed experiments are designed to characterize further conditioned drug effects in the rotational model and a related rat preparation.
The specific aims of the proposed experiments are: 1) to determine the minimal and optimal number of sessions for conditioning rotation to a drug stimulus and the number of sessions required to extinguish it, 2) to test additional drugs to determine it they can serve as effective conditioned stimuli for rotation, 3) to determine if drugs in addition to apomorphine can serve as effective unconditioned stimuli for conditioned rotation 4) to determine if drugs can block or generalize to the conditioned stimulus drug, 5) to assess the degree of context dependence of the drug stimulus 6) to test the persistence of the conditioned behavior and 7) to assess the generality of what appears to be a profound, fundamental advantage to conditioning with direct DA agonists in a DA denervated preparation by testing conditioning in whole brain DA depleted rats.
