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 e ffects in offspring and is the leading cause of mental deficiency in the We stern world. The objective of this study was to examine the effects of chro nic prenatal ethanol exposure on the number of GABA(A) receptors and relati ve protein levels for GABA(A) receptor alpha1 and beta2/3 subunits in the a dult guinea pig cerebral cortex. Timed pregnant Dunkin-Hartley strain guine a pigs were given one of the following oral treatments daily throughout ges tation: 4 gm of ethanol per kilogram of maternal body weight, isocaloric-su crose with pair feeding, or isovolumetric water with adlibitum access to fo od. The ethanol treatment resulted in a peak maternal blood ethanol concent ration of 328 +/- 55 mg/dl (71.3 +/- 12.0 mM) on gestational day 57 (term, similar to 68 d). Chronic prenatal exposure to ethanol resulted in increase d spontaneous locomotor activity throughout development and decreased cereb ral cortical weight in adult offspring. The number of cerebral cortical [H- 3] muscimol binding sites was increased in adult offspring from the ethanol treatment group, and there was a corresponding increase in the amount of G ABA(A) receptor alpha1 and beta2/3 subunit proteins in these same animals. For individual offspring, there were correlations between locomotor activit y and cerebral cortical weight, as well as between cerebral cortical weight and GABA(A) receptor neurochemistry. There was no effect of chronic prenat al ethanol exposure on [H-3] MK-801 binding in this tissue. These data demo nstrate that chronic prenatal ethanol exposure has long-term consequences o n the regulation of GABA(A) receptor expression in the cerebral cortex.