Characterization of the discriminative stimulus effects of buprenorphine in pigeons

Abstract.

Rationale: Buprenorphine is a low-efficacy mu opioid agonist that can reduce drug taking in opioid abusers; however, the mechanism by which buprenorphine modifies the actions of other drug taking and the consequences of repeated treatment with buprenorphine are not fully understood. Objective: The purposes of this study were to evaluate the time- and dose-dependence of discriminative stimulus effects in pigeons receiving buprenorphine repeatedly and to examine possible interactions between buprenorphine and heroin. Methods: Six pigeons discriminated between vehicle and 0.178 mg/kg buprenorphine while responding under an FR schedule for food. Substitution and drug combination studies characterized the potency and time course for buprenorphine, as well as interactions between buprenorphine and heroin. Results: Stimulus control by buprenorphine was maintained throughout the study and was not changed by repeated daily dosing or by an acute injection of large doses of buprenorphine. Mu opioid agonists substituted for buprenorphine with the following order of potency: heroin≥butorphanol>nalbuphine≥morphine. Ketamine, enadoline, spiradoline, amphetamine and cocaine failed to substitute completely for buprenorphine. The discriminative stimulus effects of buprenorphine lasted 2–72 h, depending on dose, and naltrexone prevented but did not reverse the effects of buprenorphine. Conclusion: Despite a very long duration of action and apparent irreversibility, under these conditions in pigeons, buprenorphine does not modulate the discriminative stimulus effects of itself or heroin. Thus, simple agonism might account for the therapeutic effectiveness of buprenorphine in opioid abusers.