Behavioral effects of cocaine alone and in combination with selective dopamine antagonists in the squirrel monkey

Abstract

Effects of cocaine, alone and in combination with the dopaminergic antagonists, SCH 23390 and haloperidol were studied in squirrel monkeys trained to respond under fixed-interval schedules of electric-shock presentation. Cocaine at intermediate doses (0.1 and 0.3 mg/kg) increased rates of responding under the fixed-interval schedule and during 1-min timeout periods that separated each fixed-interval component. Higher doses (1.0–3.0 mg/kg) decreased response rates. Cocaine also dose-dependently altered the temporal pattern of responding characteristic of behavior under fixed-interval schedules. Haloperidol (0.003–0.1 mg/kg) and SCH 23390 (0.001–0.03 mg/kg) dose-dependently decreased rates of responding. A low dose (0.001 mg/kg) of the selective D1 antagonist, SCH 23390, did not appreciably alter the effects of cocaine. Higher doses (0.003–0.01 mg/kg), which when given alone decreased rates of responding, attenuated the increases in response rates produced by cocaine. In addition, the decreases in response rates produced by the higher dose of cocaine were attenuated by 0.01 mg/kg SCH 23390. The alterations in temporal patterning of responding under the fixed-interval schedule were not antagonized by any dose of SCH 23390. Haloperidol (0.003 mg/kg) did not appreciably alter the effects of cocaine; higher doses (0.01–0.03 mg/kg), which when given alone decreased rates of responding, attenuated the increases in response rates produced by 0.1 mg/kg cocaine. The decreases in response rates under the fixed-interval schedule that were produced by higher doses, or the changes in temporal patterning of responding at any dose of cocaine, were not antagonized by any dose of haloperidol that was studied. The present results suggest that the effects of cocaine on schedule-controlled behavior in squirrel monkeys are not the exclusive domain of one dopamine receptor subtype.