Effect of chronic maternal ethanol administration on glutamate and N-methyl- d-aspartate binding sites in the hippocampus of the near-term fetal guinea pig

Abstract

The objective of this study was to determine the effect of chronic maternal administration of ethanol on hippocampal l-glutamate (glutamate) and N-methyl- d-aspartate (NMDA) binding sites in the near-term fetal guinea pig. Starting on gestational day (GD) 2, pregnant guinea pigs received one of the following oral treatments up to and including GD 62 (term, about GD 68): 4 g ethanol · kg maternal body weight −1 · day −1; isocaloric sucrose and pair-feeding; or water. Maternal blood ethanol concentration was determined at 1 h after the daily ethanol dose on GD 59. Fetuses were studied at GD 63 (mature, near-term fetus). Fetal body weight and brain weight were determined. The density ( B max) and affinity ( K d) of the glutamate and NMDA binding sites in the fetal hippocampus were measured using a radioligand membrane binding assay; saturation analysis was conducted on hippocampal synaptic membrane preparation (HSMP). Maternal blood ethanol concentration on GD 59 was 269 ± 111 (SD) mg/dl (59 ± 24 mM). There was no maternal or embryonic fetal lethality in any of the three treatment groups, and ethanol treatment did not affect maternal body weight gain compared with sucrose or water treatment. Fetal brain weight, but not body weight, was decreased in the ethanol treatment group compared with the sucrose and water treatment groups. The B max values of the glutamate and NMDA binding sites were decreased in the ethanol treatment group compared with the sucrose and water treatment groups; there was no difference in the K d values of the glutamate and NMDA binding sites among the three treatment groups. The data demonstrate that, in the guinea pig, chronic maternal administration of a binge-type ethanol regimen throughout gestation restricts brain growth and decreases the density of glutamate and NMDA binding sites in the hippocampus, as manifested in the mature fetus.