Abstract
The discriminative stimulus effects of l-α-acetylmethadol (LAAM), l-α-acetylnormethadol (nor-LAAM),l-α-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.
Footnotes
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Send reprint requests to: Dr. Charles P. France, Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, LA 70112-1393.
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↵1 This work was supported by United States Public Health Service Grant DA05018. C.P.F. is the recipient of a Research Scientist Development Award (DA00211). Animals used in these studies were maintained in accordance with the Institutional Animal Care and Use Committee, Louisiana State University Medical Center, and guidelines of the Committee on Care and Use of Laboratory Animal Resources, National Research Council [Department of Health, Education and Welfare, Publication no. (National Institutes of Health) 85–23, revised 1983].
- Abbreviations:
- % DR
- percent drug responding
- LAAM
- ℓ-α-acetylmethadol
- nor-LAAM
- ℓ-α-acetylnormethadol
- dinor-LAAM
- ℓ-α-acetyldinormethadol
- Received January 6, 1997.
- Accepted April 25, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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