The actions of opirates like heroin and morphine are mediated by three major types of opiate receptors, termed mu,delta and kappa. Subtypes of these receptors have been identified through the used of selective opiate receptor agonists andantagonists. While mu opiate receptors have clearly beenimplicated in the abuse liability of opiates and stimulants, the involvement of delta and kappa receptors has not been completely assessed. The kappa opiate receptors seem to be involved in some of the unpleasant effects of opiates and are unlikely to be involved in reinforcement. However, there are a limited number of recent studies which have indicated a potential involvement of kappa opiate receptors in the behavioral effects of cocaine. This research will utilize both site-directed acylating agents and antisence the methodologies to selectively decrease the number of delta opiate receptors. The self-administration of cocaine will be evaluated before and following the decrease in delta receptors. The proposed studies will provide an assessment of the role of kappa opiate receptors in the self-administration of cocaine and potentially increase our understanding of the neurochemistry, neurobiology and treatment of stimulant abuse.
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