Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus.
Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross-fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H] inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggest that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers.
Noble
E P
EP
Neuropsychiatric Institute, University of California, Los Angeles 90024-1759.
Ritchie
T
T
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007051:Ibotenic Acid / Q000378:metabolism; D008297:Male; D010069:Oxadiazoles / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism
D000596:Amino Acids; D010069:Oxadiazoles; D010716:Phosphatidylinositols; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D000431:Ethanol; D016318:Quisqualic Acid