Brain dopamine receptors play an important role in behavior and mediate the effects of certain abused drugs including cocaine and combinations of selected H1 antagonists and opioids (e.g., T's and Blues). Recently, two subtypes of dopamine receptors (D1 and D2) have been identified in vitro, suggesting that the role of dopamine in different behaviors and in the effects of abused drugs may involve selective effects at one type of receptor or interactions between the two types of receptors. Information regarding the role of the subtypes of dopamine receptors is of fundamental importance to our understanding of brain mechanisms in behavior. Yet, little is known regarding the interplay of D1 and D2 receptors in ongoing behavior or in the effects of abused drugs, and research in primate species is limited. In the present period, we have initiated studies of the behavioral effects of dopaminergic drugs in monkeys to specifically address these issues. Our preliminary findings already indicate that the behavioral effects of dopamine agonists differing in potency or selectivity can be markedly dissimilar. We propose to continue our investigations by systematically establishing the behavioral effects of direct agonists differing in selectivity for D1 and D2 receptors and of indirect nonselective dopamine agonists. Extension of our ongoing studies involving schedule-controlled performance, drug self-administration, drug discrimination, and unconditioned behavior to determine the effects of dopaminergic drugs differing in potency or efficacy will establish the characteristic behavioral actions of selective D1 or D2 agonists. The effects of D1 and D2 agonists after treatment with selective antagonists will allow us to evaluate the pharmacological specificity and quantitative nature of these actions. We also will study the effects of combinations of D1 and D2 agonists to evaluate the functional consequences of combined D1 and D2 receptor stimulation. Finally, we will evaluate the modification of the effects of dopaminergic drugs by the mixed-action opioid buprenorphine. The abuse of combinations of dopaminergic and opioid drugs (e.g., T's and Blues, black crack) is well-established. The results of our studies will provide important information for determining mechanisms that mediate such abuse-related effects as well as the potential therapeutic effects of buprenorphine in treatment of cocaine dependence.
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