Effects of morphine and narcotic antagonists on avoidance behavior of the squirrel monkey.

The effects of morphine, cyclazocine and nalorphine were evaluated on the continuous avoidance behavior of the squirrel monkey with schedule parameters similar to those used in previous studies on the rat. With this schedule, a lever-pressing response postponed or terminated the delivery of an electric shock to the monkey's tail. Dose-response curves were determined for each drug administered alone and in combination with 1.0 mg/kg of naloxone. In the 1st hour of a 4-hour session, avoidance responding was increased slightly by low doses of morphine and cyclazocine and was decreased by higher doses; nalorphine only increased responding at all doses tested. In hour 4 of the session, the effects of morphine were similar to those at hour 1; cyclazocine produced only a dose-related increase in response rate and nalorphine had no effect on responding. All drug effects were blocked by naloxone. The effects of these drugs in the monkey are qualitatively similar to those described for behavior maintained under similar schedule contingencies in the rat, although quantitative differences in drug effects between the two species are apparent. Nalorphine, naloxone and naltrexone were also compared in reversing the depression of avoidance behavior induced by 10 mg/kg of morphine. As antagonists of the response-rate decreasing effects of this dose of morphine, the relative potencies of naltrexone:naloxone:nalorphine were 30:10:1 in hour 1, and 100:10:1 in hour 4. The durations of action of naloxone and nalorphine were equivalent and were shorter than that of naltrexone. The potencies and durations of action for reversing morphine-induced depression of the avoidance behavior of the squirrel monkey are similar to those derived from tests involving the precipitation of abstinence by these narcotic antagonists in morphine-dependent rhesus monkeys as well as in human volunteers.