FURTHER EVALUATION OF DISCRIMINATIVE EFFECTS OF MORPHINE IN RAT

Abstract

Rats were trained in a 2 choice discrete trial avoidance paradigm to discriminate between saline and 3.0 mg/kg of morphine. Behavior was considered to be under stimulus control when the rats completed at least 90% of the trials in a 20-trial session on the morphine-appropriate choice lever after receiving morphine and when they completed at least 90% of the trials on the saline-appropriate choice lever after receiving saline. The discriminative effects of morphine, measured by responding on the morphine-appropriate lever, were then evaluated by determining the dose-response characteristics of representative narcotic analgesics, analgesics with mixed agonist and narcotic antagonist properties and nonopioid psychoactive drugs. Eight narcotic analgesics each produced dose-related responding on the morphine-appropriate lever. The relative potency for producing discriminative effects equivalent to those produced by 3.0 mg/kg of morphine ranged from etonitazene = 1000 .times. morphine to propoxyphene = 0.0175 .times. morphine. Of the narcotic antagonist analgesics tested, butorphanol and nalmexone produced discriminative effects equivalent to those of the morphine training dose whereas nalorphine, levallorphan, oxilorphan, nalbuphine and ketocyclazocine did not. The nonpioid psychoactive drugs, mescaline, ketamine, physostigmine and scopolamine, also failed to produce discriminative effects equivalent to those produced by 3.0 mg/kg of morphine. These results confirm and extend previous findings that of those drugs which were also evaluated in man, discriminative effects equivalent to the training dose of morphine are produced uniquely by narcotic analgesics and narcotic antagonists which produce morphine-like subjective effects. The hypothesis is supported that the properties of morphine which enable it to function as a discriminative stimulus in the rat are analogous to those responsible for producing subjective effects in man.