NALOXONE PRETREATMENT BLOCKS ACUTE MORPHINE-INDUCED SENSITIZATION TO NALTREXONE

The present experiment was designed to examine whether the acute sensi tization to naltrexone that is induced by a single dose of morphine co uld be blocked by pretreatment with naloxone. Food-deprived male Sprag ue-Dawley rats were trained to respond for food on a multiple-trial fi xed interval 3-min schedule. Reinforcement was contingent upon a respo nse within a 10-s limited hold period following a fixed interval of 3 min. A trial consisted of three fixed intervals separated by a 10-min timeout period during which responses were not reinforced. The rate de creasing effects of the opioid antagonist naltrexone were determined b y cumulative dosing. Pretreatment with morphine (3.0 mg/kg, SC) result ed in a 70-fold increase in sensitivity to the response rate decreasin g effect of naltrexone compared with saline pretreatment. The increase d sensitivity was dose-dependently blocked by naloxone administration 10 min before morphine. The blockade by naloxone was overcome by incre asing the pretreatment dose of morphine to 10 mg/kg. The results provi de further evidence that acute agonist-induced sensitization to the ra te-reducing effects of naltrexone is mediated by opioid receptors.