Chronic ethanol exposure alters MK-801 binding sites in the cerebral cortex of the near-term fetal guinea pig.
The mechanism of ethanol central nervous system (CNS) teratogenesis, resulting from chronic maternal ingestion of high-dose ethanol during pregnancy, is not clearly understood. One of the target sites for ethanol-induced damage in the developing brain is the cerebral cortex. It has been proposed that chronic prenatal ethanol exposure alters NMDA receptors in the developing cerebral cortex. To test this hypothesis, timed pregnant guinea pigs were administered one of the following oral treatments throughout gestation: 4 g ethanol/kg maternal body weight/day; isocaloric sucrose/pair-feeding; water; or no treatment (ad lib). Near-term fetuses were studied at gestational day (GD) 63 (term, about GD 68). This ethanol regimen produced a maternal blood ethanol concentration of 66+/-4 mM (304+/-19 mg/dl) at 1 h after the daily dose on GD 58. The chronic ethanol regimen decreased near-term fetal body weight (12-26% decrease), brain weight (23% decrease), and cerebral cortical weight (21% decrease), compared with the isocaloric sucrose/pair-feeding, and combined water/ad lib experimental groups. Saturation analysis of near-term fetal cerebral cortical membranes using a [3H]MK-801 radioligand binding assay demonstrated a decreased affinity and increased number of MK-801 binding sites for the chronic ethanol regimen compared with the control treatments. These data support the suggestion that upregulation of NMDA receptors in the cerebral cortex after chronic prenatal ethanol exposure could lead to NMDA receptor-mediated excitotoxicity in this brain region.
Chiu
J
J
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Brien
J F
JF
Wu
P
P
Eubanks
J H
JH
Zhang
L
L
Reynolds
J N
JN
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D006168:Guinea Pigs; D008431:Maternal-Fetal Exchange; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016291:Dizocilpine Maleate