Cocaine and related stimulant drugs of abuse can be conceived as pharmacological rewards, whose addictive or behaviorally-reinforcing actions are mediated via a dopaminergic brain reward system. Although it is accepted that stimulants enhance the release or block the reuptake of dopamine, the relative importance and specific roles of the two main dopamine receptor subtypes, D1 and D2, in stimulant reinforcement remain unclear. The recent availability of highly selective and fully efficacious D1 and D2 agonists allow direct tests for the first time of four current hypotheses of dopamine receptor subtype involvement in stimulant reinforcement. The reinforcing properties of these agonists--and their ability to be selectively antagonized by D1 and D2 receptor blockade--will be measured in three behavioral assays of positive reinforcement: drug self-administration, conditioned reinforcement of operant behavior, and conditioned place preference. Elucidation of the roles of dopamine receptor subtypes in stimulant reinforcement will increase our understanding of endogenous reinforcement mechanisms, and will enhance the development of safe and effective medications for detoxification and the pharmacological treatment of cocaine addiction.
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