Effects of neonatal or maternal methadone administration on ornithine decarboxylase activity in brain and heart of developing rats

Abstract

Methadone was administered daily to pregnant or nursing rats, or directly to neonates, and the effects on brain and heart weights and ornithine decarboxylase (ODC) activities were determined during postnatal development. Exposure to methadone in the postnatal period either directly or via the mother resulted in delays in maturational decreases in brain ODC accompanied by deficits in brain weight. Prenatal exposure alone had less effect on brain weight or ODC but appeared to enhance the effect of subsequent methadone exposure during the postnatal period. In the heart, direct methadone exposure or prenatal plus postnatal maternal administration led to a pattern of altered ODC activity consistent with delayed development, accompanied by heart weight deficits. The disturbance of heart ODC development after purely prenatal or purely postnatal maternal exposures differed from that obtained after direct administration to the neonate. These data show that exposure to methadone during fetal and/or neonatal life produces alterations in polyamine metabolism which may result in abnormal organ development. The type of change is dependent upon the period and route of exposure and may reflect both direct effects on the pup and indirect effect from drug-induced alterations in maternal metabolism or behavior.