Chronic prenatal ethanol exposure increases GABA(A) receptor subunit protein expression in the adult guinea pig cerebral cortex.

Excessive consumption of ethanol during pregnancy can produce teratogenic effects in offspring and is the leading cause of mental deficiency in the Western world. The objective of this study was to examine the effects of chronic prenatal ethanol exposure on the number of GABA(A) receptors and relative protein levels for GABA(A) receptor alpha1 and beta2/3 subunits in the adult guinea pig cerebral cortex. Timed pregnant Dunkin-Hartley strain guinea pigs were given one of the following oral treatments daily throughout gestation: 4 gm of ethanol per kilogram of maternal body weight, isocaloric-sucrose with pair feeding, or isovolumetric water with ad libitum access to food. The ethanol treatment resulted in a peak maternal blood ethanol concentration of 328 +/- 55 mg/dl (71.3 +/- 12.0 mm) on gestational day 57 (term, approximately 68 d). Chronic prenatal exposure to ethanol resulted in increased spontaneous locomotor activity throughout development and decreased cerebral cortical weight in adult offspring. The number of cerebral cortical [(3)H]muscimol binding sites was increased in adult offspring from the ethanol treatment group, and there was a corresponding increase in the amount of GABA(A) receptor alpha1 and beta2/3 subunit proteins in these same animals. For individual offspring, there were correlations between locomotor activity and cerebral cortical weight, as well as between cerebral cortical weight and GABA(A) receptor neurochemistry. There was no effect of chronic prenatal ethanol exposure on [(3)H]MK-801 binding in this tissue. These data demonstrate that chronic prenatal ethanol exposure has long-term consequences on the regulation of GABA(A) receptor expression in the cerebral cortex.