Phencyclidine (PCP) self-administration and withdrawal in rhesus monkeys: effects of buprenorphine and dizocilpine (MK-801) pretreatment

Abstract

The effects of dizocilpine and buprenorphine pretreatment on behavior reinforced by orally delivered phencyclidine (PCP) and saccharin, and on PCP withdrawal-induced disruptions in food-maintained responding were examined. Sixteen male rhesus monkeys were used in six different experimental protocols. Two groups of monkeys (N = 4-5) self-administered PCP (0.25 mg/ml) and water under concurrent FR 16 schedules, and were pretreated with IM injections of saline, and dizocilpine (0.001-0.1 mg/kg), or buprenorphine (0.003-0.8 mg/kg) 30 min before the 3-h sessions for 5 days. Two other groups (N = 5) were treated similarly except they had access to saccharin (0.03% or 0.3% w/v) and water under concurrent FR 16 schedules. In two other groups (N = 3), the effects of saline, dizocilpine (0.005-0.1 mg/kg), or buprenorphine (0.2 and 0.8 mg/kg) pretreatment were studied on PCP (0.25 mg/ml) withdrawal-induced disruptions in food-maintained responding. Dizocilpine and buprenorphine reduced both PCP (0.25 mg/ml) and saccharin (0.03% or 0.3% w/v) self-administration, especially at the 0.1-mg/kg dizocilpine dose and 0.2-mg/kg buprenorphine dose. Dizocilpine attenuated the PCP withdrawal effect, but buprenorphine had no effect on behavioral disruptions induced by PCP withdrawal. When dizocilpine was administered 2 days after PCP withdrawal began, the withdrawal effects were almost completely reversed. These results suggest that although drugs from the same and different pharmacological classes can suppress self-administration of drug and nondrug reinforcers, the same doses may produce an opposite effect or no effect on food-maintained behavior during PCP withdrawal.