title: In contrast to cocaine, prenatal exposure to methadone does not produce detectable alterations in the developing mouse brain.
abstract: Whereas prenatal cocaine exposure dramatically alters brain development, the safety of methadone in detoxification programs for heroin-addicted pregnant women is uncertain. This paper compares the effects of exposure to methadone or to cocaine in utero on a model system, the developing mouse brain. Methadone (40 mg/kg/day, i.e., 40-fold detoxification dosage) or cocaine (30 mg/kg/day, as in severe addiction) was injected into mice from day 8 to day 18 of gestation. Pre- and postnatal brain development was analyzed at the anatomical and microscopical levels, including by immunostaining of post-mitotic cells, neurites, and astrocytes. Prenatal mice exposure to cocaine caused neuronal misaddressing among neocortical layers, abnormal gliogenesis, and defective neuritic outgrowth and bundling. Methadone produced small-for-date offspring with normal brain development. In conclusion, supratherapeutic methadone doses induce intrauterine growth retardation in mice, but spare brain cytoarchitecture. In contrast, cocaine produces less growth retardation, but severely disturbs neocortical layering.
authors.affiliation: Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, Louvain University Medical School, 75, Avenue Hippocrate, B-1200, Brussels, Belgium. nassogne@cell.ucl.ac.be
authors.forename: M C
authors.initials: MC
authors.lastname: Nassogne
authors.forename: P
authors.initials: P
authors.lastname: Gressens
authors.forename: P
authors.initials: P
authors.lastname: Evrard
authors.forename: P J
authors.initials: PJ
authors.lastname: Courtoy
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000534:rehabilitation; D003712:Dendrites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D006556:Heroin Dependence / Q000534:rehabilitation; D006801:Humans; D008691:Methadone / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects
chemical_list: D003042:Cocaine; D008691:Methadone