THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Copyright 1983 by The American Society for Pbarmacologj, and Experimental Therapeutics Tolerance to Phencyclidine in Pigeons: Cross-Tolerance to

In order to determine whether tolerance developed to the behav-ioral effects of phencydidine, 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 (0.1-1 0 mel/kg i.m.), ketamine (3-56 mol/kg i.m.) and pentobarbital (1-75,mol/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. re-sponding at immediate doses. At higher doses, pentobarbital decreased responding. High doses of phencyclidine and keta-mine 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,mol/kg/day i.m.), dose-response curves were redetermined for all three drugs. A toler-ance was observed for moderate doses of phencyclidine, and a moderate cross-tolerance was observed to ketamine. No toler-ance 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 ob-served. After 21 5 days of daily phencyclidine administration, no withdrawal signs were observed upon the discontinuation of daily injections. Phencyclidine has been shown to increase the rate of re-sponding at low to moderate doses and decrease responding at higher doses in mice, rats, pigeons and monkeys responding under fixed- or variable-interval schedules of food presentatio