Behavioral effects of phencyclidine and ketamine alone and in combination with other drugs

The behavioral effects of phencyclidine (PCP) and ketamine administered alone and in combination with naloxone, atropine, methyl atropine, chlorpromazine and d-amphetamine were studied in squirrel monkeys trained to press a response lever under a fixed-ratio 30 schedule maintained by the termination of a stimulus associated with electric shock presentation. Under non-drug conditions, a period of high-rate responding in the presence of the stimulus associated with shock presentation was followed by a period of no responding during a 40-s timeout scheduled between fixed-ratio components. Mean rates of responding during fixed-ratio components decreased monotonically as PCP dose increased from 0.1 to 0.56 mg/kg, and doses of 3.0 and 5.6 mg/kg ketamine produced decreases in mean response rate comparable to doses of 0.3 and 0.56 mg/kg PCP. The dose-effect functions revealed that ketamine was approximately one-tenth as potent as PCP. The present data also characterized the time-course effects of PCP and ketamine, with the former having effects that were slower in onset yet more persistent in time. None of the drugs studied in combination with PCP and ketamine provided evidence of a pharmacological antagonism of the behavioral effects of the latter two drugs. Rather, the data indicated an enhancement of behavioral effects when certain drug combinations were studied.