Increased sensitivity to rate-altering and discriminative stimulus effects of morphine following continuous exposure to naltrexone.

Two experiments evaluated whether termination of a continuous infusion of naltrexone altered sensitivity to the rate-suppressing or discriminative stimulus effects of morphine in rats. An 8-day infusion of saline or doses of 3, 10, or 18 mg/kg/day naltrexone did not alter rates of lever pressing maintained under fixed-ratio 30 schedules of food delivery. A dose of 10 mg/kg day naltrexone produced insurmountable antagonism of the rate-suppressing and analgesic effects of morphine. The ED50 of morphine for rate suppression decreased by 2-fold 1 day after termination of the 8-day infusion of 10 or 18 mg/kg/day naltrexone. The ED50 of morphine returned to initial values within 8 days. Termination of infusion of either saline or 3 mg/kg/day naltrexone did not alter the ED50 of morphine. Changes in morphine stimulus control were evaluated in rats trained to discriminate saline and 3.2 mg/kg morphine under fixed-ratio 15 schedules of food delivery. The ED50 of morphine for stimulus control or rate suppression decreased by 2-fold 1 day after termination of an 8-day infusion of 18 mg/kg/day naltrexone. The ED50 of morphine for rate suppression returned to initial values within 3 days; that for stimulus control, within 5 days. Thus, termination of exposure to high doses of naltrexone produced brief changes in sensitivity to the rate-altering and discriminative stimulus effects of morphine that parallel reported changes in sensitivity to the analgesic and lethal effects of morphine.