Effects of quinpirole and SKF 38393 alone and in combination in squirrel monkeys trained to discriminate cocaine.

Abstract

The present study was designed to assess the behavioral similarity of the effects of prototype dopamine receptor-subtype selective agonists and cocaine. Squirrel monkeys (N = 4) were trained with food reinforcement to press one of two levers after administration of IV cocaine (0.3 mg/kg) or the other lever after saline. After training, IV cocaine produced reliable responding on the cocaine lever (greater than 98%), whereas saline produced reliable responding on the alternate lever (greater than 98%). The D2 agonist, quinpirole (0.003-1.0 mg/kg, IM), produced dose-related increases in cocaine-appropriate responding, with maximal effects of 62%. When delivered IV, quinpirole (0.01-0.17 mg/kg) was approximately twice as potent, but no more effective. The D1 agonist, SKF 38393 (0.3-30.0 mg/kg, IM or 3.0-17.0 mg/kg, IV) failed to produce any significant cocaine-appropriate responding. Further, pretreatment with SKF 38393 (either 0.3 or 10.0 mg/kg, IM) did not significantly alter the the quinpirole (0.01-1.0 mg/kg, IM) dose-effect curve. The effects of these drugs differ from those previously reported in rats, suggesting a species difference that may be of importance in evaluating the behavioral pharmacology of cocaine.