Behavioral effects of fetal and neonatal exposure to methadone in the rat.

Twenty-two pregnant Sprague-Dawley rats were maintained on methadone hydrochloride solution (14 mg/kg/day, PO, ad lib) throughout gestation, or served as prenatal controls with equal intake of tap water. Within 48 hr of birth 129 pups were cross-fostered to dams of postnatal control or methadone (27 mg/kg/day, PO, ad lib) status. A significant increase in stillbirths occurred among prenatal methadone litters. Disturbed maternal behavior sometimes developed when a dam was switched from prenatal control to postnatal methadone or vice versa. Foster pups of such females showed long-lasting growth retardation and less emotionality in Open Field trials as adults. They were less active on Day 28 in a circular path test, but when tested after Day 65, they were more active. Pups exposed to methadone both pre- and post-natally were lest active in initial Open Field tests (both on Day 28 and after Day 65) of all treatment groups. No severe withdrawal symptoms were noted in pups at birth or weaning. The effect of methadone on growth, emotionality and activity level was mild compared to the effects of drug-induced maternal disorganization.