The effects of acute and chronic phencyclidine on schedule-controlled behavior in the squirrel monkey

The effects of acute and chronic administration of phencyclidine (PCP) were examined in five male squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation. Acute PCP (0.01-0.60) mg/kg i.m.) produced dose-related decreases in response rate during both components of the schedule. Both components were equally affected by the drug. The effects of the drug on fixed-interval response rate were dependent on the control rate of responding in corresponding segments of the interval. After the initial dose-response determination, the subjects were placed on an individualized regimen of chronic PCP administration lasting from 82 to 126 days, beginning with daily injections for 2 days alternating with saline injections for 2 days, progressing to four injections daily. No evidence of physical dependence was seen upon withdrawal of the drug. Redetermination of the dose-response function for PCP (0.03-1.0 mg/kg i.m.) demonstrated a nearly 2-fold shift to the right of both the fixed-interval and fixed-ratio dose-response curves, indicating tolerance. In addition, the subjects' behavior recovered sooner from a dose of PCP (0.60 mg/kg i.m.) given after the chronic regimen than from the same dose given before the chronic regimen. The results demonstrate that tolerance can occur to the behavioral effects of PCP in the squirrel monkey.