Discriminative stimulus and response rate-decreasing effects of kappa opioids: Antagonism by naloxone

Abstract

The present study examined the discriminative stimulus and response rate-decreasing effects of kappa opioids in pigeons trained to discriminate a 0.017 mg/kg dose of bremazocine from saline. Bremazocine, spiradoline, C1977, U69, 593 and U50, 488 substituted completely for the bremazocine stimulus in a dose-dependent and naloxone-reversible manner. Apparent pA 2 values (range, 6.01–6.81) of naloxone against the descriminative stimulus effects of these kappa opioids were smaller than those reported previously in the pigeon for naloxone against the discriminative stimulus effects of various mu opioids. Bremazocine, C1977, soiradoline and U69, 593 also decreased rate of responding in a dose-dependent and naloxone-reversible manner. The apparent pA 2 values (range, 6.25–6.44) for naloxone against the rate-decreasing effects of bremazocine, C1977 and U69, 593 were not different from the apparent pA 2 values for naloxone against their discriminative stimulus effects. An apparent pA 2 for naloxone against the rate-decreasing effects of spiradoline could not be determined due to the shallow slope of the Schild plot. 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-decreasing effects of some kappa opioids are mediated by similar mechanisms and that a non-opioid mechanism may contribute to the rate-decreasing effects of spiradoline and U50, 488.