Alcohol: effects on GABAA receptor function and gene expression.

Chronic ethanol treatment increased the binding of [3H]Ro15-4513 in cerebral cortex and cerebellum of rats and produced a reduction in the alpha 1, alpha 2, alpha 5 GABAA receptor subunits mRNAs in the cerebral cortex and alpha 1 subunit mRNA in the cerebellum, and an increase in alpha 6 subunit mRNA in the cerebellum. An increase in the alpha 6 subunit mRNA which selectively encodes Ro15-4513 binding in the cerebellum is consistant with an increase in the photolabelling of [3H]Ro15-4513 to the 55 KDa band in the cerebellum of chronic ethanol treated rats. Using polyclonal antibodies, we have confirmed that chronic ethanol treatment decreased alpha 1 subunit (51 KDa), alpha 2 subunit (53 KDa) and alpha 3 subunit (59 KDa) in cerebral cortex. These results suggest that chronic ethanol treatment produces a decrease in the expression of GABAA receptor subunit which may underlie a molecular basis for ethanol tolerance.