Behavioral dependence upon phencyclidine and ketamine in the rat.

Continuous intravenous infusion of phencyclidine (PCP) in rats induced dependence, shown by disrupted lever-pressing behavior during withdrawal. After 10 days of PCP infusion at 0.5 mg/kg/hr, response rates dropped markedly within 6 to 12 hours and recovered within 24 to 48 hours in four rats. Re-administering PCP during withdrawal reversed the rate decline, and ketamine at 2.5 mg/kg/hr also reversed PCP withdrawal effects, indicating cross-dependence. Withdrawal from continuous ketamine infusion similarly reduced response rates in three rats, demonstrating that both drugs can produce dependence.

Study at a glance

Abstract

The present studies examined whether dependence could be induced by continuous i.v. infusion of phencyclidine (PCP) in rats as demonstrated by disruptions of operant behavior during withdrawal. Rats were trained to lever press for their daily food rations under fixed-ratio 30 schedules of reinforcement during four, daily, 0.5-hr sessions. In the first study, withdrawal from 10 days of PCP infusion at a rate of 0.5 mg/kg/hr resulted in markedly reduced response rates which typically occurred within 6 to 12 hr and recovered within 24 to 48 hr, providing evidence of dependence in the four rats tested. The PCP withdrawal effect was replicated systematically in seven additional rats which had been given individually maximally tolerated PCP infusion regimens. Additionally, when PCP was readministered during withdrawal, the downward trend in response rates was halted and rates increased rapidly to control levels, providing evidence of reversal of PCP withdrawal effects. When ketamine, another arylcyclohexylamine dissociative anesthetic, was administered during PCP withdrawal at a dose of 2.5 mg/kg/hr, it also was able to reverse PCP withdrawal effects, demonstrating cross-dependence from PCP to ketamine. Response rates were also reduced markedly relative to control levels during withdrawal from continuous i.v. ketamine infusion in three rats tested, providing evidence that dependence upon this drug could also be induced. Withdrawal of PCP and ketamine administration can disrupt operant behavior, providing further evidence for the ability of these drugs to produce dependence.