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, result ing from chronic maternal ingestion of high-dose ethanol during pregnancy, is not clearly understood. One of the target sites for ethanol-induced dama ge in the developing brain is the cerebral cortex. It has been proposed tha t 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; wate r; 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 b lood ethanol concentration of 66 +/- 4 mM (304 +/- 19 mg/dl) at 1 h after t he daily dose on GD 58. The chronic ethanol regimen decreased near-term fet al 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 [H-3]MK-801 radioli gand binding assay demonstrated a decreased affinity and increased number o f MK-801 binding sites for the chronic ethanol regimen compared with the co ntrol treatments. These data support the suggestion that upregulation of NM DA receptors in the cerebral cortex after chronic prenatal ethanol exposure could lead to NMDA receptor-mediated excitotoxicity in this brain region. (C) 1999 Elsevier Science Inc. All rights reserved.