Naloxone pretreatment blocks acute morphine-induced sensitization to naltrexone.
The present experiment was designed to examine whether the acute sensitization to naltrexone that is induced by a single dose of morphine could be blocked by pretreatment with naloxone. Food-deprived male Sprague-Dawley rats were trained to respond for food on a multiple-trial fixed interval 3-min schedule. Reinforcement was contingent upon a response 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 decreasing effects of the opioid antagonist naltrexone were determined by cumulative dosing. Pretreatment with morphine (3.0 mg/kg, SC) resulted in a 70-fold increase in sensitivity to the response rate decreasing effect of naltrexone compared with saline pretreatment. The increased sensitivity was dose-dependently blocked by naloxone administration 10 min before morphine. The blockade by naloxone was overcome by increasing the pretreatment dose of morphine to 10 mg/kg. The results provide further evidence that acute agonist-induced sensitization to the rate-reducing effects of naltrexone is mediated by opioid receptors.
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.
D
D
White-Gbadebo
S
S
Holtzman
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule
D009270:Naloxone; D009271:Naltrexone; D009020:Morphine