Tolerance to phencyclidine in pigeons: cross-tolerance to ketamine.

In order to determine whether tolerance developed to the behavioral effects of phencyclidine, pigeons were trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of food presentation. When rates and patterns of responding reached stability, dose-response curves for phencyclidine (0.1-10 mumol/kg i.m.), ketamine (3-56 mumol/kg i.m.) and pentobarbital (1-75 mumol/kg i.m.) were determined. Phencyclidine, ketamine and pentobarbital all decreased fixed-ratio 30 responding in a dose-related manner and increased fixed-internal 600-sec. responding at immediate doses. At higher doses, pentobarbital decreased responding. High doses of phencyclidine and ketamine suppressed responding in the early portions of the session, but when responding returned, it returned at a high rate. After 35 daily injections of phencyclidine (3 mumol/kg/day i.m.), dose-response curves were redetermined for all three drugs. A tolerance was observed for moderate doses of phencyclidine, and a moderate cross-tolerance was observed to ketamine. No tolerance was observed for the total suppression of responding produced by high doses of phencyclidine and ketamine early in the test sessions. No cross-tolerance to pentobarbital was observed. After 215 days of daily phencyclidine administration, no withdrawal signs were observed upon the discontinuation of daily injections.