Differential Regulation of GABAA Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Previous research has shown that chronic ethanol consumption dramatically alters GABA(A) receptor alpha1 and alpha4 subunit gene expression in the cerebral cortex and GABA(A) receptor alpha1 and alpha6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GABA(A) receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABA(A) receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABA(A) receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABA(A) receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABA(A) receptor alpha4 subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABA(A) receptor alpha1, alpha2, alpha3, beta(2/3), or gamma2 was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABA(A) receptor alpha4 subunits and significantly decreased the relative expression of cerebral cortical GABA(A) receptor alpha1 subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABA(A) receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.