DISCRIMINATIVE STIMULUS AND RESPONSE RATE-DECREASING EFFECTS OF KAPPA-OPIOIDS - ANTAGONISM BY NALOXONE

The present study examined the discriminative stimulus and response ra te-decreasing effects of kappa opioids in pigeons trained to discrimin ate a 0.017 mg/kg dose of bremazocine from saline. Bremazocine, spirad oline, CI977, U69,593 and U50,488 substituted completely for the brema zocine stimulus in a dose-dependent and naloxone-reversible manner. Ap parent pA(2) values (range, 6.01-6.81) of naloxone against the discrim inative stimulus effects of the kappa opioids were smaller than those reported previously in the pigeon for naloxone against the discriminat ive stimulus effects of various mu opioids. Bremazocine, CI977, spirad oline and U69,593 also decreased rate of responding in a dose-dependen t and naloxone-reversible manner. The apparent pA(2) values (range, 6. 25-6.44) for naloxone against the rate-decreasing effects of bremazoci ne, CI977 and U69,593 were not different from the apparent pA(2) value s for naloxone against their discriminative stimulus effects. An appar ent pA(2) for naloxone against the rate-decreasing effects of spiradol ine could not be determined due to the shallow slope of the Schild plo t. Although the rate-decreasing effects of U50,488 were antagonized by naloxone, the degree of antagonism was small and not dose-dependent. These findings indicate that the discriminative stimulus and rate-decr easing effects of some kappa opioids are mediated by similar mechanism s and that a non-opioid mechanism may contribute to the rate-decreasin g effects of spiradoline and U50,488.