DISCRIMINATIVE STIMULUS EFFECTS OF L-ALPHA-ACETYLMETHADOL (LAAM), BUPRENORPHINE AND METHADONE IN MORPHINE-TREATED RHESUS-MONKEYS

The discriminative stimulus effects of I-alpha-acetylmethadol (LAAM), I-alpha-acetylnormethadol (nor-LAAM), I-alpha-acetyldinormethadol (din or-LAAM), buprenorphine and methadone were investigated in morphine-tr eated (3.2 mg/kg/day) rhesus monkeys (n = 3-6) discriminating between saline and naltrexone (0.01 mg/kg) and responding under a fixed ratio (FR) schedule of stimulus-shock termination, Monkeys responded on the naltrexone lever after either the administration of 0.01 mg/kg of nalt rexone or the substitution of saline for the daily dose of morphine (i .e., 27-hr morphine deprived). Morphine dose-dependently reversed nalt rexone lever responding in morphine-deprived monkeys. Methadone, LAAM, nor-LAAM and dinor-LAAM had morphine-like discriminative stimulus eff ects in all monkeys, whereas, buprenorphine had naltrexone-like discri minative stimulus effects in three monkeys and morphine-like effects i n two monkeys; 24 hr after administration, buprenorphine antagonized t he effects of morphine in the former and antagonized the effects of na ltrexone in the latter, The agonist and antagonist effects of buprenor phine persisted for more than 6 days. The relative duration of action was: buprenorphine > LAAM > nor-LAAM = methadone = dinor-LAAM = morphi ne. That buprenorphine had markedly different discriminative stimulus effects in monkeys treated identically with morphine is likely due to the low efficacy of buprenorphine and emphasizes the difficulty in pre dicting the behavioral effects of buprenorphine in opioid-dependent in dividuals. The considerably longer duration of LAAM, than either nor-L AAM or dinor-LAAM, indicates that the rate of metabolite formation is important for the long duration of LAAM and further suggests that vari ations in metabolic activity among individuals might result in differe nces in the behavioral effects of LAAM.