CHRONIC ETHANOL ADMINISTRATION REGULATES THE EXPRESSION OF GABA(A) RECEPTOR ALPHA(1) AND ALPHA(5) SUBUNITS IN THE VENTRAL TEGMENTAL AREA AND HIPPOCAMPUS

Ethanol dependence and tolerance involve perturbation of GABAergic neu rotransmission. Previous studies have demonstrated that ethanol treatm ent regulates the function and expression of GABA(A) receptors through out the CNS. Conceivably, changes in receptor function may be associat ed with alterations of subunit composition. In the present study, a co mprehensive (1-12 weeks) ethanol treatment paradigm was used to evalua te changes in GABA(A) receptor subunit expression in several brain reg ions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippoc ampus (a region involved in memory/cognition). Expression of alpha(1) and alpha(5) subunits was regulated by ethanol in a region-specific an d time-dependent manner. Following 2-4 weeks of administration, cortic al and cerebellar alpha(1) and alpha(5) subunit immunoreactivity was r educed. In the VTA, levels of alpha(1) subunit immunoreactivity were s ignificantly decreased after 12 weeks but not 1-4 weeks of treatment. Hippocampal alpha(1) subunit immunoreactivity and mRNA content were al so significantly reduced after 12 but not after 4 weeks of treatment. In contrast, alpha(5) mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABA(A ) receptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effe cts of alcohol.