ANTAGONISM OF THE RESPONSE RATE DECREASING EFFECTS OF MEPERIDINE AND MORPHINE BY BETA-FUNALTREXAMINE AND NALTREXONE IN SQUIRREL-MONKEYS

Lever pressing by squirrel monkeys was maintained under a fixed-ratio 30 schedule of food presentation. The response rate-decreasing effects of meperidine and morphine were examined alone and in combination wit h several doses of the irreversible, mu-selective opioid antagonist be ta-funaltrexamine and the reversible, opioid antagonist naltrexone. be ta-Funaltrexamine alone decreased response rates to greater than 50% o f central at all doses in two of the four monkeys and at the highest d ose in one monkey. In the monkeys in which beta-funaltrexamine decreas ed rates, beta-funaltrexamine either did not shift the meperidine or t he morphine dose-effect curve or it shifted these curves to the left. In the monkeys in which beta-funaltrexamine alone did not decrease rat es, it shifted the meperidine and the morphine dose-effect curves to t he right. Naltrexone also shifted both the meperidine and morphine dos e-effect curves rightward, although not in a dose-dependent manner. Th ese data suggest that the rate-decreasing effects of meperidine and mo rphine in squirrel monkeys are altered by beta-funaltrexamine and nalt rexone in a similar manner, providing additional evidence that the rat e-decreasing effects of both meperidine and morphine an mediated by mu -opioid receptors. (C) 1997 Elsevier Science Ireland Ltd.