Discriminative stimulus effects of l-alpha-acetylmethadol (LAAM), buprenorphine and methadone in morphine-treated rhesus monkeys.

The discriminative stimulus effects of l-alpha-acetylmethadol (LAAM), l-alpha-acetylnormethadol (nor-LAAM), l-alpha-acetyldinormethadol (dinor-LAAM), buprenorphine and methadone were investigated in morphine-treated (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 naltrexone or the substitution of saline for the daily dose of morphine (i.e., 27-hr morphine deprived). Morphine dose-dependently reversed naltrexone lever responding in morphine-deprived monkeys. Methadone, LAAM, nor-LAAM and dinor-LAAM had morphine-like discriminative stimulus effects in all monkeys, whereas, buprenorphine had naltrexone-like discriminative stimulus effects in three monkeys and morphine-like effects in two monkeys; 24 hr after administration, buprenorphine antagonized the effects of morphine in the former and antagonized the effects of naltrexone in the latter. The agonist and antagonist effects of buprenorphine persisted for more than 6 days. The relative duration of action was: buprenorphine > LAAM > nor-LAAM = methadone = dinor-LAAM = morphine. 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 predicting the behavioral effects of buprenorphine in opioid-dependent individuals. The considerably longer duration of LAAM, than either nor-LAAM or dinor-LAAM, indicates that the rate of metabolite formation is important for the long duration of LAAM and further suggests that variations in metabolic activity among individuals might result in differences in the behavioral effects of LAAM.