Effects of naloxone, diprenorphine, buprenorphine and etorphine on unpunished and punished food-reinforced responding in the squirrel monkey.

The effects of naloxone and three oripavine derivatives, diprenorphine, an antagonist, buprenorphine, a mixed agonist-antagonist, and etorphine, an agonist, were examined on food-reinforced responding in squirrel monkeys. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response produced a brief electric shock to the tail. Daily sessions were 1 hr. Responding in the two components was not differentially affected by any of the drugs. Naloxone decreased responding in both components only slightly at high doses (ED50 greater than 10 mg/kg). In contrast, the three oripavines produced prominent dose-related decreases in responding with the following order of potency for the nonpunishment component: etorphine (ED50 = 0.0005 mg/kg) greater than buprenorphine (ED50 = 0.02 mg/kg) greater than diprenorphine (ED50 = 0.11 mg/kg). Etorphine had a short duration of action (approximately 1 hr) whereas the actions of diprenorphine (1.0 mg/kg) and buprenorphine (0.1 mg/kg) persisted for 24 to 48 hr. Concurrent administration of naloxone (0.1 and 1.0 mg/kg) antagonized the response rate-decreasing effects of etorphine and buprenorphine in a dose-dependent manner (i.e., dose-response curves were shifted to the right) but failed to block the effects of diprenorphine. Although all three oripavines produced comparable decreases in food-reinforced responding, there are qualitative as well as quantitative differences between the drugs. Diprenorphine appears to act through a different mechanism from that of buprenorphine and etorphine.