Premium
Chronic ethanol treatment and GABA A receptor a6 subunit gene expression: a study using a6 subunit‐deficient mice
Author(s) -
Vekovischeva Olga Y.,
UusiOukari Mikko,
Korpi Esa R.
Publication year - 2000
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2000.tb00216.x
Subject(s) - protein subunit , cerebellum , downregulation and upregulation , receptor , ethanol , medicine , endocrinology , gene expression , chemistry , gene , pharmacology , biology , microbiology and biotechnology , biochemistry
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 b‐galactosidase enzyme and an unfunctional truncated α6 subunit under the control of the α6 gene promoter. Chronic ethanol treatment failed to alter the cerebellar b‐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.