Effects of continuous infusions of SCH 23390 on cocaine- or food-maintained behavior in rhesus monkeys.

Rhesus monkeys were trained to press a lever in daily experimental sessions under a three-component multiple schedule of reinforcement. In the first and third components, food was available under a fixed-ratio (FR) 30 schedule. In the second component cocaine (0.025-0.10 mg/kg/injection, i.v.) was available under a FR 30 schedule. There was a brief time-out period after each reinforcer was delivered. When responding was stable, monkeys received continuous (24 h/day) i.v. infusions of several doses of SCH 23390 (0.8-6.4 mg/kg/day) for at least the same number of sessions as was required for responding to decline to low levels when saline was available for self-administration. In two of four monkeys, SCH 23390 produced larger decreases in responding maintained by cocaine than in responding maintained by food. The effects of SCH 23390 on drug- and/or food-maintained responding progressively diminished over several days of continuous infusion such that, at the end of the infusion period, responding approximated control rates. Termination of daily infusions of SCH 23390 caused minimal effects on food-maintained responding, whereas in three of four monkeys decreases in responding maintained by cocaine were observed. These latter effects were greater following exposure to the higher doses. Following recovery from these effects, consistently higher rates of responding were maintained by doses of cocaine on the ascending limb of the dose-response function. These results suggest that a D(1) antagonist may decrease the reinforcing effects of cocaine. However, these effects diminish over time and exposure to SCH 23390 may result in long-lasting enhancement of sensitization to the reinforcing effects of cocaine.