Chronic alcohol administration increases the expression of
cerebellum-specific GABA_A receptor α6 subunit mRNA, protein and
selective autoradiographical fingerprint on rat and mouse brain
sections. We have tested whether the α6 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
β-galactosidase enzyme and an unfunctional truncated α6 subunit under
the control of the α6 gene promoter. Chronic ethanol treatment failed to
alter the cerebellar β-galactosidase activity when compared with no
treatment and isocaloric sucrose treatment in groups of α6
subunit-deficient mice. The results suggest that tolerance to
motor-impairing effects of ethanol can be achieved in the absence of α6
subunit-containing GABA_A receptors, but that the reported upregulation
of α6 gene transcription by ethanol treatment requires functional α6
subunits.