IN CONTRAST TO COCAINE, PRENATAL EXPOSURE TO METHADONE DOES NOT PRODUCE DETECTABLE ALTERATIONS IN THE DEVELOPING MOUSE-BRAIN

Whereas prenatal cocaine exposure dramatically alters brain developmen t, the safety of methadone in detoxification programs for heroin-addic ted pregnant women is uncertain. This paper compares the effects of ex posure to methadone or to cocaine in utero on a model system, the deve loping mouse brain. Methadone (40 mg/kg/day, i.e., 40-fold detoxificat ion dosage) or cocaine (30 mg/kg/day, as in severe addiction) was inje cted into mice from day 8 to day 18 of gestation. Pre- and postnatal b rain development was analyzed at the anatomical and microscopical leve ls, including by immunostaining of post-mitotic cells, neurites, and a strocytes. Prenatal mice exposure to cocaine caused neuronal misaddres sing among neocortical layers, abnormal gliogenesis, and defective neu ritic outgrowth and bundling. Methadone produced small-for-date offspr ing with normal brain development. In conclusion, supratherapeutic met hadone doses induce intrauterine growth retardation in mice, but spare brain cytoarchitecture. In contrast, cocaine produces less growth ret ardation, but severely disturbs neocortical layering. (C) 1998 Elsevie r Science B.V. All rights reserved.