Regional variations in the effects of chronic ethanol administration on GABA(A) receptor expression: potential mechanisms

Gamma-aminobutyric acid type A (GABA_A) receptors in brain adapt to chronic ethanol exposure via changes in receptor function and subunit expression. The present review summarizes currently available data regarding changes in GABA_A receptor subunit mRNA and peptide expression. Data are presented from various different brain regions and the variations between specific brain regions used to draw conclusions about mechanisms that may underlie GABA_A receptor adaptations during chronic ethanol exposure. In the whole cerebral cortex, chronic ethanol exposure leads to a reduction of GABA_A receptor 1 subunit mRNA and peptide levels and a near equivalent increase in 4 subunit mRNA and peptide levels. This observation is the primary support for the hypothesis that altered receptor composition is a mechanism for GABA_A receptor adaptation produced by chronic ethanol exposure. However, other brain regions do not display similar patterns of subunit changes. Moreover, subregions within cortex (prefrontal, cingulate, parietal, motor, and piriform) exhibit patterns of changes in subunit expression that differ from whole cortex. Therefore, regional differences in GABA_A receptor subunit expression are evident following chronic ethanol administration, thus suggesting that multiple mechanisms contribute to the regulation of GABA_A receptor expression. These mechanisms may include the involvement of other neurotransmitter systems, endogenous steroids and second or third messenger cross-talk.