Phencyclidine-like discriminative stimulus properties of opioids in the squirrel monkey

Abstract

The opioids SKF 10047, dl-cyclazocine, and dextrorphan have been shown to have phencyclidine (PCP)-like discriminative stimulus properties in the rat. In order to extend the generality of this observation, the stimulus effects of these and other opioids were evaluated in squirrel monkeys trained to discriminate between IM injections of saline and 0.25 mg/kg of PCP in a two-choice discrete-trial avoidance paradigm. Stimulus control of behavior was characterized by the reliable completion of at least 22 trials of a 25-trial session on the appropriate choice lever after an injection of saline or PCP. In tests of stimulus generalization, SKF 10047, d-cyclazocine, dextrorphan, normetazocine, dl-cyclazocine, l-cyclazocine, and dextromethorphan occasioned dose-related increases in PCP-appropriate responding. The first four of these compounds and, under some conditions, l- and dl-cyclazocine, produced stimulus control of behavior comparable to that produced by the PCP training dose. Six other opioids occasioned responding only on the saline-appropriate lever: ethylketocyclazocine, ketocyclazocine, levorphanol, levallorphan, pentazocine, naltrexone. Naltrexone (1.0 or 4.0 mg/kg) attenuated slightly the PCP-like stimulus effects of SKF 10047 and dextrorphan, but increased PCP-appropriate responding with l- and dl-cyclazocine and levorphanol by enabling higher doses of these drugs to be tested without disruption of responding. The PCP-like stimulus effects of certain opioids appear to be mediated at neuronal substrates acted upon by PCP rather than at sites typically associated with opiate activity. These neuronal sites of action common to opioids and PCP may correspond to the sigma “opiate” receptor.