Role of testosterone in ethanol- and morphine-induced increases in the alcohol dehydrogenase-dependent metabolism of ethanol in the male rat

T. J. Cicero, K. S. Newman, P. F. Schmoeker, E. R. Meyer

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Abstract

The present studies were undertaken to examine the previously suggested hypothesis that ethanol and morphine increase the alcohol dehydrogenase (ADH)-dependent metabolism of ethanol in the male rodent by depressing serum testosterone levels. In agreement with previous studies, castration in our studies markedly increased liver ADH activity and the in vivo metabolism of ethanol in the male Sprague-Dawley rat; both effects of castration were completely prevented by silastic implants of testosterone. Our studies concerning the role of testosterone in the effects of morphine on the ADH-dependent metabolism of ethanol can be summarized as follows. First, during chronic morphine administration, testosterone reversed the effects of morphine on the ADH-dependent metabolism of ethanol during very early stages of treatment, but thereafter became much less effective. Second, upon cessation of chronic morphine administration, serum testosterone levels rapidly returned to control levels (<4 days), whereas nearly 14 days were required for the complete recovery of liver ADH activity. Finally, testosterone failed to reverse the increase in the ADH-dependent metabolism of ethanol produced by the combination of chronic morphine administration and castration. In our chronic ethanol studies, we found that chronic ethanol treatment (14 days) markedly lowered serum testosterone levels and also increased liver ADH activity and the in vivo ethanol metabolic rate. Testosterone silastic implants completely reversed ethanol-induced decreases in serum testosterone levels, but were only modestly effective in preventing the effects of the drug on the ADH-dependent metabolism of ethanol. Thus, the present data conflict with previous reports and argue against the hypothesis that testosterone mediates the effects of ethanol and the opiates on the ADH-dependent metabolism of ethanol.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume222
Issue number1
StatePublished - Jan 1 1982

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