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.