Behavioral effects of chronic phencyclidine administration in rats

The development of tolerance to phencyclidine (PCP) was examined in rats using behavioral rating scales with simultaneous measurements of locomotor activity, stereotyped behaviors, and ataxia. Significant tolerance to the stereotyped behaviors and ataxia induced by 5 or 10 mg/kg PCP was found on day 5 of chronic drug treatment. Because ataxia interferes with PCP-induced locomotor activity (Sturgeon et al. 1979), tolerance to PCP-induced ataxia produced an increase in locomotor activity on day 5. Tolerance to the ataxia, but not to the stereotyped behaviors induced by PCP, was more prominent after day 15 of PCP administration than after day 5. Administration of PCP for 15 days resulted in significant decrease in locomotor activity for the 5 mg/kg group but not for the 10 mg/kg group. These results suggest that behavioral tolerance, rather than supersensitivity, develops after chronic PCP administration. The effects of PCP returned to baseline over a 14-day withdrawal period for rats treated with 5 mg/kg PCP for 15 days. Rats treated with 10 mg/kg PCP for 15 days still had not returned to baseline when tested 28 days after cessation of PCP treatment.