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 chroni c ethanol exposure via changes in receptor function and subunit expression. The present review summarizes currently available data regarding changes i n GABA(A) receptor subunit mRNA and peptide expression. Data are presented from various different brain regions and the variations between specific br ain regions used to draw conclusions about mechanisms that may underlie GAB A(A) receptor adaptations during chronic ethanol exposure. In the whole cer ebral cortex, chronic ethanol exposure leads to a reduction of GABA(A) rece ptor alpha 1 subunit mRNA and peptide levels and a near equivalent increase in alpha 4 subunit mRNA and peptide levels. This observation is the primar y support for the hypothesis that altered receptor composition is a mechani sm for GABA(A) receptor adaptation produced by chronic ethanol exposure. Ho wever, other brain regions do not display similar patterns of subunit chang es. Moreover, subregions within cortex (prefrontal, cingulate, parietal, mo tor, and piriform) exhibit patterns of changes in subunit expression that d iffer from whole cortex. Therefore, regional differences in GABA(A) recepto r subunit expression are evident following chronic ethanol administration, thus suggesting that multiple mechanisms contribute to the regulation of GA BA(A) receptor expression. These mechanisms may include the involvement of other neurotransmitter systems, endogenous steroids and second or third mes senger cross-talk. (C) 2000 Elsevier Science Ltd. All rights reserved.