Discriminative effects of morphine in the squirrel monkey

Abstract

Squirrel monkeys were trained in a two-choice discrete trial avoidance task to discriminate between intramuscular injections of saline and 3.0 mg/kg of morphine. Morphine (0.1-10 mg/kg) produced a dose-related increase in the number of trials completed on the morphine-appropriate lever. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) morphine-like stimulus control was produced by all other narcotic analgesics tested (fentanyl, oxymorphone, levorphanol, methadone and meperidine); 2) in so doing, these drugs spanned a 900-fold potency range relative to morphine; 3) stimulus control was blocked by the specific narcotic antagonist naloxone; and 4) stereospecificity was a requirement for stimulus control--levorphanol produced stimulus control equivalent to 3.0 mg/kg of mrophine but its optical isomer dextrorphan did not. The time course of the stimulus control produced by 3.0 mg/kg of morphine showed that the animals continued to respond on the morphine-appropriate lever up to 14 hours after morphine administration. In contrast, monkeys administered 0.01 mg/kg of fentanyl responded on the morphine lever for only as lone as 1/2 hour after fentanyl administration. Naloxone, d-amphetamine and pentobarbital all failed to substitute for morphine, Thus, this study has extended previous observations of the discriminative properties of morphine in rats by demonstrating that qualitatively similar data are produced in a second species, the squirrel monkey.