Discriminative stimulus effects of buprenorphine in the rat

Buprenorphine, a potent "low efficacy" or "partial" morphine-like opioid agonist, has morphine-like discriminative effects in animals and humans discriminating morphine or a related drug. The purpose of the present study was to characterize further the discriminative effects of buprenorphine in subjects trained to discriminate buprenorphine itself. Rats trained to discriminate between SC injections of saline and either 0.03 or 0.1 mg/kg buprenorphine generalized completely to morphine and to other morphine-like agonists. These drugs were approximately 3 times more potent in the rats trained with 0.03 mg/kg buprenorphine than in those trained with 0.1 mg/kg; however, the potency of buprenorphine itself did not differ significantly between groups. Indicative of efficacy differences among mixed-action opioids, rats discriminating 0.03 mg/kg buprenorphine generalized completely to butorphanol and pentazocine and partially to nalbuphine, whereas those discriminating 0.1 mg/kg generalized completely to butorphanol, partially to pentazocine, and little to nalbuphine. Stimulus control of behavior by 0.1 mg/kg buprenorphine was blocked surmountably by low doses of antagonists, stereoselective, and pharmacologically selective. These results are consistent with those of other studies showing that the discriminative effects of buprenorphine are morphine-like and mediated by the mu-opioid receptor, and extend the conditions under which this has been demonstrated to stimulus control maintained by buprenorphine itself.