The characterization of factors that contrbute to the onset and persistence of compulsive drug-seeking behavior is crucual for the constrution of effective treatment strategies for drug abuse. Likewise, the determination of the mechanisms through which these factors interact with this behavior is petinent to the development of potential pharmacotherapeutic agenits. The experiments described in this proposal are designes to investigate the interaction between stressful environmental stimuli, adrenocorticosteroids stimulus effects of cocaine and therefore may provide a substrate through which the environment may influence this behavior. Four specific amis designes to test this hypothesis are outlines in this proposal. The purpose of the experiments proposed in Specific Aim 1 is to determine the role of Type I and Type II adrenocorticosteroid receptors in the favilitation on intravenous cocaine self-administration by cortocosterone. The role of corticosterone in the determinative stimulus of cocaine and in the stressor-induced generalization to cocaine will be investigated in Specific Aim 2 using the corticosterone synthesis inhibitor, keteconzole.
Specific Aim3 consists of experiments desgined to assess the reinstatement of cocaine self-administration by a conditioned stressor following chronic extinction. The role of corticosterone in this reinstatement will be investigated using ketoconozole. Changes in Type I and Type II receptors following chronic cocaine self-administration will be investigated in experiments proposed in Specific Aim 4.
