Antagonism of the response rate-decreasing effects of meperidine and morphine by beta-funaltrexamine and naltrexone in squirrel monkeys.

Abstract

Level 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 with several doses of the irreversible, mu-selective opioid antagonist beta-funaltrexamine and the reversible, opioid antagonist naltrexone. beta-Funaltrexamine alone decreased response rates to greater than 50% of control at all doses in two of the four monkeys and at the highest dose in one monkey. In the monkeys in which beta-funaltrexamine decreased rates, beta-funaltrexamine either did not shift the meperidine or the morphine dose-effect curve or it shifted these curves to the left. In the monkeys in which beta-funaltrexamine alone did not decrease rates, it shifted the meperidine and the morphine dose-effect curves to the right. Naltrexone also shifted both the meperidine and morphine dose-effect curves rightward, although not in a dose-dependent manner. These data suggest that the rate-decreasing effects of meperidine and morphine in squirrel monkeys are altered by beta-funaltrexamine and naltrexone in a similar manner, providing additional evidence that the rate-decreasing effects of both meperidine and morphine are mediated by mu-opioid receptors.