OPIOIDS AND RATE OF POSITIVELY REINFORCED BEHAVIOR - DIFFERENTIAL ANTAGONISM BY NALTREXONE

Lever pressing by rats was maintained under a fixed-ratio 30 schedule of food presentation. The response rate-decreasing effects of several opioid compounds that vary in selectivity for, and activity at, mu,kap pa, and non-opioid receptors, were examined alone and in combination w ith the opioid antagonist naltrexone. Naltrexone (0.01-1.0 mg/kg) prod uced dose-dependent and generally parallel rightward shifts in the dos e-effect curves for morphine, fentanyl, butorphanol and nalbuphine. Ap parent pA(2) values for naltrexone against these agonists ranged from 7.05 to 7.29, and the slopes of the regression lines fitted to the Sch ild plots approximated theoretical unity (-1.0), suggesting a competit ive interaction at mu-opioid receptors. In contrast, although at least one dose of naltrexone (0.01-10.0 mg/kg) antagonized the response rat e-decreasing effects of bremazocine, U50,488, (-)-pentazocine and nalo rphine, suggesting some opioid activity, these effects differed from t hose of the mu agonists in that: (a) they were less sensitive to naltr exone antagonism; (b) maximal rightward shifts were smaller; (c) antag onism patterns were not directly related to naltrexone dose and, in so me cases, were influenced by the response rate-decreasing effects of t he larger naltrexone doses; and (d) there were considerable between-su bjects differences in sensitivity to naltrexone antagonism. Naltrexone (0.1-10.0 mg/kg) did not antagonize the effects of the non-opioid con trol compound pentobarbital. The present results suggest that patterns of naltrexone antagonism can provide a basis for making inferences ab out receptor activity related to the effects of some opioids on rate o f schedule-controlled behavior. With some opioids, however, such infer ences are limited by the direct response rate-decreasing effects of na ltrexone itself and by differences in patterns of antagonism across su bjects.