ACUTE AND CHRONIC EFFECTS OF NALTREXONE AND NALOXONE ON SCHEDULE-CONTROLLED BEHAVIOR OF SQUIRREL-MONKEYS AND PIGEONS

Abstract

Dose-effect curves were obtained for the influence of naltrexone, of naloxone and of morphine on lever-pressing responses of squirrel monkeys and key-pecking responses of pigeons maintained by food presentation during fixed-interval (FI) and fixed-ratio (FR) components of a multiple schedule. Morphine caused dose-related decreases in FI and FR responding, with complete suppression occurring after 3 mg/kg was administered to monkeys and after 10 mg/kg was administered to pigeons. Naltrexone doses as low as 0.03 mg/kg (monkeys) or 0.1 mg/kg (pigeons) and naloxone doses as low as 0.1 mg/kg (monkeys) or 1 mg/kg (pigeons) shifted morphine dose-effect curves by one or more log units to the right. The effects of a 3 mg/kg injection of morphine were completely blocked by naltrexone (0.1-0.3 mg/kg) injected more than 2 h before morphine. Naltrexone was 3-10 times more potent than naloxone as an antagonist of morphine was longer acting. Given alone, only high doses of naltrexone or naloxone (10 mg/kg, monkeys; 56 mg/kg, pigeons) had pronounced actions; FR and Fl responding were markedly decreased and vomiting often occurred. Repeated daily injections of these high doses of naltrexone or naloxone resulted in little or no tolerance. After termination of chronic treatment 1-6 mo., dose-effect curves for naltrexone on FR and FI responding maintained by food presentation were shifted markedly to the left with the monkeys, but not with the pigeons.