Three-choice drug discrimination: phencyclidine-like stimulus effects of opioids

To assess the commonalities and differences in the discriminative stimulus properties of phencyclidine (PCP) and psychotomimetic opioids, rats were trained to discriminate PCP (2.0 mg/kg), cyclazocine (1.0 mg/kg), and saline in a three-choice discrete-trial avoidance paradigm. Stimulus control of behavior, defined as the reliable completion of 18 trials of a 20-trial session on the appropriate choice lever after administration of PCP, cyclazocine, or saline, was established in an average of 157 sessions. In tests of stimulus generalization, SKF-10,047 and dextrorphan engendered lever choices appropriate to both PCP and cyclazocine, sometimes in the same animal and at the same dose. The rats responded almost exclusively on the PCP-appropriate lever after ketamine and on the saline lever after morphine and d-amphetamine, indicating pharmacologic specificity. Naltrexone, in doses that had little effect on stimulus control of behavior by PCP, completely blocked cyclazocine-like stimulus control. Decreases in cyclazocine choices in the presence of naltrexone were associated with increases in PCP choices. These results support conclusions derived from two-choice procedures that psychotomimetic opioids have PCP-like stimulus effects, and provide direct evidence that these effects of cyclazocine are mediated by a component of action insensitive to an opiate antagonist.