ACUTE SUPERSENSITIVITY TO THE DISCRIMINATIVE STIMULUS EFFECTS OF NALTREXONE IN PIGEONS

Abstract

The ability of acute morphine injections to augment discriminative stimulus effects and rate-decreasing effects of opioid antagonists was examined in pigeons trained to discriminate among i.m. injections of morphine (5.6 mg/kg), saline and naltrexone (10.0 mg/kg). A single injection of 10.0 or 32.0 mg/kg of morphine 24 hr before naltrexone produced 3- and 10-fold decreases, respectively, in the dose of naltrexone required for complete generalization. When morphine (10.0-100.0 mg/kg) was administered 48 hr before naltrexone, pigeons were not more sensitive to naltrexone as a discriminative stimulus but continued to be more sensitive to the rate-decreasing effects of naltrexone. Conditions that produced the largest increase in sensitivity to the discriminative stimulus effects of naltrexone (32.0 mg/kg of morphine 24 hr before the session) also increased sensitivity to the discriminative stimulus effects and rate-decreasing effects of naloxone, but did not affect the discriminative stimulus effects of diprenorphine, nalorphine or morphine. Increases in sensitivity to the discriminative stimulus effects of naltrexone and naloxone after single injections of morphine approached in magnitude the increases reported previously in pigeons treated chronically (once/daily) with large doses of morphine. However, the lack of generalization to naltrexone after pretreatment with still larger doses of morphine, as well as the failure of nalorphine and diprenorphine to substitute for naltrexone as discriminative stimuli under conditions in which sensitivity to naltrexone was increased, support the view that naltrexone does not produce its discriminative stimulus effects in nondependent animals exclusively through an opioid antagonistic action. The results suggest that morphine-induced, acute supersensitivity to the discriminative stimulus effects of naltrexone differs from the supersensitivity to antagonists observed during chronic morphine treatment.