DIFFERENTIAL EXPRESSION OF GABA(A) BENZODIAZEPINE RECEPTOR SUBUNIT MESSENGER-RNAS AND LIGAND-BINDING SITES IN MOUSE CEREBELLAR NEURONS FOLLOWING IN-VIVO ETHANOL ADMINISTRATION - AN AUTORADIOGRAPHIC ANALYSIS

The gamma-aminobutyric acid(A) (GABA(A))/benzodiazepine (BZ) receptor is a pentamer composed of subunits belonging to several classes (alpha (1-6), beta(1-4), gamma(1-4), delta and rho 1 and rho(2)). In situ hyb ridization, radioligand autoradiography, and immunocytochemistry were used to examine GABA(A)/BZ receptor alpha(1), alpha(6), beta(2), beta( 3) and gamma(2) subunit expression in murine Purkinje, granule, and de ep cerebellar neurons after in vivo ethanol exposure. Chronic ethanol treatment resulted in decreased alpha(1) subunit mRNA expression in ea ch cell type, whereas the expression of alpha(6) and gamma(2) subunit mRNA levels increased; no changes were observed in the expression of b eta(2) and beta(3) subunit mRNA. GABA and BZ agonist binding and antib ody staining paralleled the changes in mRNA levels. Acute ethanol inje ction resulted in increased expression of alpha(1) and beta(3) mRNAs, whereas levels of alpha(6), beta(2) and gamma(2) mRNAs remained stable . Our results indicate that, in cerebellar neurons, the expression of specific GABA(A)/BZ receptor subunit mRNAs, polypeptides, and binding sites is independently regulated by in vivo administration of alcohol. The observed changes were not restricted to any one cerebellar cell t ype, because subunit expression in Purkinje, granule, and deep cerebel lar cells was similarly affected.