Chronic ethanol administration regulates the expression of GABA(A) receptor α1 and α5 subunits in the ventral tegmental area and hippocampus

Abstract

Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABA(A) receptors throughout the CNS. Conceivably, changes in receptor function may be associated with alterations of subunit composition. In the present study, a comprehensive (112 weeks) ethanol treatment paradigm was used to evaluate changes in GABA(A) receptor subunit expression in several brain regions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippocampus (a region involved in memory/cognition). Expression of α1 and α5 subunits was regulated by ethanol in a region-specific and time-dependent manner. Following 2-4 weeks of administration, cortical and cerebellar α1 and α5 subunit immunoreactivity was reduced. In the VTA, levels of α1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1-4 weeks of treatment. Hippocampal α1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, α5 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 effects of alcohol.