Self-administration of an enkephalin analog by rhesus monkey.
Intravenous injections of a synthetic enkephalin analog, FK-33-824 were found to maintain operant responding under second-order schedule control (FR 4[VR 16:S]) in five, morphine-dependent rhesus monkeys. All monkeys self-administered enkephalin in amounts equivalent to morphine at comparable doses per injection. Each of five doses of enkephalin (0.5, 0.25, 0.125, 0.05 and 0.01 mg/kg/inj) were substituted for morphine during 10 consecutive sessions over a 56 hr period. No monkey developed opiate withdrawal signs during enkephalin substitution except at the lowest enkephalin dose (0.01 mg/kg/inj). Although the number of enkephalin injections self-administered increased as the dose per injection progressively decreased, there was a significant linear decrease (p less than 0.05) in mg/kg/enkephalin per session at doses of 0.25 mg/kg/inj and below. Reductions in morphine dose per injection, over a range of 0.5 to 0.125 mg/kg/inj produced comparable increases in number of injections per session, but no significant changes in morphine intake. The number of food pellets earned on a second order FR 4 (VR 16:S) schedule decreased during enkephalin substitution. These decreases were significant at the highest doses of enkephalin (0.5 to 0.125 mg/kg/inj). These data attest to the reinforcing characteristics of an enkephalin analog in rhesus monkey and suggest that natural polypeptides may contribute to the reinforcing properties of opiate drugs.
D000818:Animals; D004327:Drinking Behavior; D004723:Endorphins / Q000008:administration & dosage*; D004745:Enkephalins / Q000008:administration & dosage*; D005247:Feeding Behavior; D000882:Haplorhini; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D012055:Reinforcement Schedule; D012646:Self Administration
D004723:Endorphins; D004745:Enkephalins; D009020:Morphine