Chronic ethanol treatment and GABAA receptor α6 subunit gene expression:: a study using α6 subunit-deficient mice

Chronic alcohol administration increases the expression of cerebellum-specific GAB AA receptor alpha 6 subunit mRNA, protein and selective autoradiographical finger print on rat and mouse brain sections. We have tested whether the alpha 6 gene is activated by chronic alcohol administration (daily p.o. injection of 2 g/kg during the first 3 days and 2.5 g/kg during the next 17 days) that produced tolerance in the rotarod test to motor impairment by acute challenge of ethanol (2 g/kg, i.p.). We utilized a mouse line engineered to express E. coli beta-galactosidase enzyme and an unfunctional truncated alpha 6 subunit under the control of the alpha 6 gene promoter. Chronic ethanol treatment failed to alter the cerebellar beta-galactosidase activity when compared with no treatment and isocaloric sucrose treatment in groups of alpha 6 subunit-deficient mice. The results suggest that tolerance to motor-impairing effects of ethanol can be achieved in the absence of alpha 6 subunit-containing GAB AA receptors, but that the reported upregulation of alpha 6 gene transcription by ethanol treatment requires functional alpha 6 subunits.