Acute and subchronic effects of methadone on the blood hormonal levels of pregnant and nonpregnant Charles River CD-1 mice.

Blood levels of ACTH, FSH, and estriol were measured throughout the estrous cycle and estriol was determined at different stages during pregnancy in Charles River CD-1 mice treated with 10 mg/kg/day of methadone or vehicle (physiological saline). Animals received one dose in a constant volume (10 ml/kg) per day subcutaneously of either methadone or saline. Blood samples of nonpregnant mice were collected 1 hour after the first dose for acute effects and 1 hour after the last dose treatment for subchronic effects. The acute administration of methadone in nonpregnant mice produced an increase in ACTH level throughout the estrous cycle whereas subchronic treatment reduced ACTH level by 51%. Acute treatment did not alter the estriol or FSH levels whereas subchronic treatment significantly lowered estriol by 17% and FSH by 79%. Methadone injected beginning on day 1 of gestation and continued through day 15 did not produce any effect on maternal body weight or food consumption but resulted in an increase in resorption sites and decrease in implantation sites. The estriol levels in control pregnant mice were 19.8, 54.8, and 109.1 ng/ml on days 1, 10, and 15 of gestation, respectively. A significant reduction of 18.8% and 35.2% in estriol was associated with methadone treatment by days 10 and 15 of gestation, respectively. Methadone, by affecting several hormonal levels in both pregnant and nonpregnant CD-1 mice, may be responsible for some of the adverse effects on reproduction encountered in this species.