DIFFERENTIAL REGULATION OF GABA(A) RECEPTOR GENE-EXPRESSION BY ETHANOL IN THE RAT HIPPOCAMPUS VERSUS CEREBRAL-CORTEX

Previous research has shown that chronic ethanol consumption dramatica lly alters GABA(A) receptor alpha(1) and alpha(4) subunit gene express ion in the cerebral cortex and GABA(A) receptor alpha(1) and alpha(6) subunit gene expression in the cerebellum. However, it is not yet know n if chronic ethanol consumption produces similar alterations in GABA( A) receptor gene expression in other brain regions. One brain region o f interest is the hippocampus because it has recently been shown that a subset of GABA(A) receptors in the hippocampus is responsive to phar macologically relevant concentrations of ethanol, Therefore, we direct ly compared the effects of chronic ethanol consumption on GABA(A) rece ptor subunit gene expression in the hippocampus and cerebral cortex. F urthermore, we investigated whether the duration of ethanol consumptio n (14 or 40 days) would influence regulation of GABA(A) receptor gene expression in these two brain regions. Chronic ethanol consumption pro duced a significant increase in the level of GABA(A) receptor alpha(4) subunit peptide in the hippocampus following 40 days but not 14 days, The relative expression of hippocampal GABA(A) receptor alpha(1), alp ha(2), alpha(3), beta(2/3), or gamma(2) was not altered by either peri od of chronic ethanol exposure, In marked contrast, chronic ethanol co nsumption for 40 days significantly increased the relative expression of cerebral cortical GABA(A) receptor alpha(4) subunits and significan tly decreased the relative expression of cerebral cortical GABA(A) rec eptor alpha(1) subunits. This finding is consistent with previous resu lts following 14 days of chronic ethanol consumption, Hence, chronic e thanol consumption alters GABA(A) receptor gene expression in the hipp ocampus but in a different manner from that in either the cerebral cor tex or the cerebellum, Furthermore, these alterations are dependent on the duration of ethanol exposure.