Behavioral effects of chronically administered cocaine in squirrel monkeys.

Cocaine (0.1 or 0.3 mg/kg/h) was infused continuously from osmotic minipumps during 14-day periods in three squirrel monkeys trained under a fixed-interval schedule of stimulus-shock termination. Chronic exposure to 0.1 mg/kg/h cocaine increased response rates during control sessions for two subjects, and rates returned to pre-infusion levels after the osmotic minipumps were removed. During chronic administration with 0.3 mg/kg/h cocaine, tolerance developed to the gross behavioral effects observed initially in all subjects and to the rate-suppressing effects observed in one subject. Using a cumulative-dosing procedure, cocaine was administered IV acutely once per week before, during and after each chronic administration with cocaine. The acute effects of cocaine on schedule-controlled responding before chronic administration and during chronic exposure to 0.1 and 0.3 mg/kg/h cocaine were similar, providing no evidence of sensitization or tolerance.