Comparison of opioid self-injection and disruption of schedule-controlled performance in the baboon

Eight opioid agonist, mixed agonist/antagonist or antagonist compounds were compared in baboons. In the first experiment, i.v. drug self-injection procedures involved a fixed-ratio schedule with a 3 hr time-out after each injection. Doses of a test drug were substituted for cocaine for 12 or 15 days. Codeine, morphine, butorphanol, nalbuphine and pentazocine all maintained self-injection above vehicle control levels. These compounds differed in their relative potencies, and morphine did not maintain maximal drug self-injection rates. Buprenorphine maintained self-injection in only one of four baboons, and SKF-10,047 and naloxone did not maintain self-injection. In a second experiment, another group of baboons responded on a fixed-ratio 50 schedule of food pellet delivery. Intravenous injections were given 30 min before test sessions that lasted 30 min. All eight drugs produced dose-related decreases in response rates, and the buprenorphine dose-response curve was more shallow and not parallel to the others. Comparison across experiments suggested that the failure of morphine to maintain maximal self-injection rates is due to its relatively high potency in suppressing schedule-controlled performance. The results of this study confirm those of previous studies demonstrating that opioids with morphine-like subjective effects in man are self-administered by laboratory animals.