Disruption of primate social behavior by d-amphetamine and cocaine: Differential antagonism by antipsychotics

Abstract

Psychostimulants lead to withdrawal from social interactions and to a decline of affective behavior in squirrel monkeys. These changes, in addition to motor stereotypies, may be related to stimulant-induced psychosis in humans. In the first of two series of experiments, 1 mg/kg d-amphetamine or 10 mg/kg cocaine, administered orally three times over 24 h to one adult male member of an established group (n=6–9), engendered stereotyped movements of the head and hands, reduced rest postures, and greatly reduced all forms of social initiatives. Chlorpromazine (0.25–1.0 mg/kg), haloperidol (0.25, 0.5 mg/kg), and physostigmine (0.04, 0.08 mg/kg), administered before the third amphetamine or cocaine injection, blocked the motor stereotypies and hyperactivity. Chlorpromazine, haloperidol, and physostigmine did not reliably antagonize the pronounced reduction in social behavior. The second series of experiments focused on agonistic behavior in the context of resident-intruder confrontations and on affiliative behavior toward group members. d-Amphetamine (3×0.5 mg/kg) and, to a lesser extent, cocaine (3×10 mg/kg) decreased affiliative and agonistic behavior. Chlorpromazine (0.5, 1.0 mg/kg) and haloperidol (0.1, 0.25 mg/kg) did not block the severe disruption of the affiliative and agonistic behavior in amphetamine-treated monkeys; physostigmine (0.06 mg/kg) reversed the decline in time spent close to the familiar monkey in amphetamine-treated monkeys. By contrast, stimulant-induced stereotypies were effectively antagonized by chlorpromazine, haloperidol, and physostigmine. These results suggest that psychostimulant-induced changes in primate social behavior may be mediated by mechanisms other than those underlying motor stereotypies.