To investigate the role of D1 dopamine receptors in the discriminative stimulus effects of cocaine, two rhesus monkeys were trained in a two-lever, food-reinforced, drug discrimination paradigm to discriminate cocaine (0.2 mg/kg, IM) from saline. Administration of various doses of cocaine resulted in a dose-related increase in the percentage of responses that occurred on the drug-appropriate lever. Administration of the D1 antagonist SCH 23390 20 min before cocaine reduced drug-appropriate responding from 100% to 0% in all subjects and increased by 4-8-fold the cocaine dose necessary to induce drug-appropriate responding. A mutual antagonism of the rate-decreasing effects of cocaine and SCH 23390 was also observed. These findings suggest that D1 receptors play a significant role in the discriminative stimulus and rate-decreasing effects of cocaine.
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