Cross-tolerance and mu agonist efficacy in pigeons treated with LAAM or buprenorphine.
The mechanism responsible for decreased opioid use during opioid substitution therapy is not fully understood. To examine whether l-alpha-acetylmethadol (LAAM) or buprenorphine attenuate behavioral effects of opioids through cross-tolerance, discriminative stimulus effects of high and low efficacy mu agonists were examined following 3- or 7-day treatment with LAAM or buprenorphine in pigeons discriminating between saline and heroin or between saline and buprenorphine, respectively. Heroin, buprenorphine and nalbuphine occasioned high levels of drug-appropriate responding in both groups; kappa opioids and non-opioids occasioned predominantly saline-appropriate responding. Administration of LAAM (3.2 mg/kg) or buprenorphine (3.2 mg/kg) occasioned predominantly heroin- or buprenorphine-appropriate responding, respectively. After discontinuation of LAAM treatment, the potency in occasioning heroin-key responding was markedly decreased for nalbuphine, slightly decreased for buprenorphine, and unchanged for heroin. Following discontinuation of buprenorphine treatment, the potency in occasioning buprenorphine-key responding was decreased for nalbuphine and unchanged for buprenorphine and heroin. Thus, greater cross-tolerance developed from LAAM and buprenorphine to low efficacy mu agonists as compared to a higher efficacy agonist. Failure of LAAM and buprenorphine treatment to modify the effects of heroin, under conditions that attenuate the effects of lower efficacy mu opioids, provides a possible rationale for why heroin abuse persists in some patients receiving large doses of agonists in substitution therapy.
Galici
R
R
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA. ruggero.galici@vanderbilt.edu
McMahon
L R
LR
France
C P
CP
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002047:Buprenorphine / Q000494:pharmacology*; D010856:Columbidae; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D003932:Heroin / Q000494:pharmacology; D008692:Methadyl Acetate / Q000494:pharmacology*; D009266:Nalbuphine / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D012965:Sodium Chloride; D003932:Heroin; D009266:Nalbuphine; D008692:Methadyl Acetate