The effects of different schedules of methadone treatment on rat brain development

The effect of maternally administered methadone (5 mg/kg, dl-methadone-HCl) on brain development of offspring treated during gestation and/or lactation was studied in the rat. Methadone treatment did not have a pronounced effect on prenatal development, but alterations in preweaning body and brain growth were observed in all drug-exposed pups. Rat pups subjected to methadone during gestation or lactation were the most severely affected, with reductions in brain (12 and 30%, respectively) and cerebellar (27 and 29%, respectively) weights recorded at weaning (Day 21). All methadone groups weighed less than controls from birth to Day 21, but brain: body weight ratios were comparable. On Day 60, cerebellar weight and brain length of the gestation-exposed group were less than control values, whereas rats given methadone throughout gestation and lactation were lighter in weight and had smaller cerebella. These results indicate that perinatal methadone exposure has a detrimental affect on neuroontogeny, with the neurobiological response governed by the timing and duration of opioid treatment. In addition, our findings suggest that disturbances in brain growth may occur after cessation of methadone exposure.