Effects of in utero ethanol exposure on the developing dopaminergic system in rats.
Previous studies from this and other laboratories suggest that dopamine is decreased in selected brain regions of postnatal rats exposed to ethanol in utero. The present study expands previous work by examining the effects of in utero ethanol exposure on dopamine D1 and D2 binding sites and dopamine uptake in postnatal rats. In addition, dopamine content in the brain stem and frontal cortex of fetal and neonatal rats was examined. The experimental results indicate that in utero ethanol exposure markedly affects the postnatal development of the dopaminergic system in the striatum and frontal cortex. We observed a marked, transient deficiency of striatal dopamine (greater than 40% decrease at 19 days) and dopamine uptake sites (approximately 25% decrease in Vmax at 35 days). The Bmax for striatal dopamine D1 binding sites was decreased by greater than 20% at both 19 and 35 days. Cortical D1 sites were markedly decreased at 19 days (greater than 40%). In contrast, the number of striatal D2 receptors was unaffected by in utero ethanol exposure at both ages. Analysis of tissue from neonatal rats demonstrated a marked dopamine deficiency in ethanol-exposed rats on postnatal day 5. In light of the proposed morphogenic actions of dopamine early in development, it is possible that the early dopamine deficiency contributes to the abnormal postnatal development of the dopaminergic system.
Druse
M J
MJ
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Tajuddin
N
N
Kuo
A
A
Connerty
M
M
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000378:metabolism; D007700:Kinetics; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism
D001552:Benzazepines; D011954:Receptors, Dopamine; D000431:Ethanol; D004298:Dopamine