Effect of Methadone Treatment During Pregnancy on the Fetal Testes and Hypothalamus in Rats

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Abstract
Animal and human data showed that methadone (M) treatment in adults causes a significant decrease in blood testosterone (T) levels. Whether M treatment of rats during pregnancy will affect fetal T levels is the subject of this study. M treatment (5 mg/kg BW [body weight]) of rats from Day 14-19 of gestation causes a significant decrease (P < 0.05) in fetal blood T and .delta.4-androstenedione (.delta.4-AD) levels in males. Higher M dose levels (7.5, 10 and 20 mg/kg BW) caused no further significant decreases in T and .delta.4-AD levels. M treatment had no effect on T and .delta.4-AD levels in female fetuses. The abilities of the fetal testes to synthesize T and of the hypothalamus to aromatize T to estrogen (E) were not affected by M treatment (10 mg/kg BW). The specificity of the M effect on male fetal T and .delta.4-AD levels was confirmed because naloxone (anti-M drug) antagonized the M effect. The decrease in male fetal T and .delta.4-AD levels in M-treated mothers apparently is not due to a direct effect of M on the fetal testes but to an indirect effect mediated elsewhere.