Effects of SKF-10047 in the phencyclidine-dependent rat: evidence for common receptor mechanisms.

The repeated administration of phencyclidine (PCP, 72 mg/kg/day) to rats led to physical dependence, as evidenced by a withdrawal syndrome exhibited approx. 24-48 h following suspension of drug. All components of the withdrawal syndrome were suppressed by s.c. injections of PCP (16 mg/kg), (+/-)-N-allylnormetazocine (SKF-10047, 16 mg/kg) and (+)-SKF-10047 (16 mg/kg), but not by injections of saline or (-)-SKF-10047. Moreover, tolerance to the behavioral effects of PCP, as well as cross-tolerance to (+/-)-SKF-10047 and (+)-SKF-10047 were observed. These data indicate that PCP and the sigma opiate SKF-10047 share mechanisms of action, which are mediated by the (+)-isomer of the sigma agonist.