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Chunk #49 — Chronic administration of ethanol — Alterations in GABAA receptor subunit expression, localization, and trafficking

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The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress.
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The development of ethanol dependence is associated with alterations in many of the functional properties of GABAA receptors throughout the brain which is attributed to altered expression or composition of GABAA receptors on the cell surface. Chronic ethanol administration differentially alters the expression of distinct GABAA receptor subunit mRNA and peptide levels in various brain regions (Table 3). The levels of GABAA receptor α1, α2, and α3 subunit mRNA/peptides are reduced in the cerebral cortex while α4, β1, β2, β3, γ1, and γ2 subunit mRNA/peptide levels are increased in cerebral cortex following chronic ethanol exposure. Since GABAA receptor α1 subunits are the most abundant subunit in the cerebral cortex, the reduction in the expression of this subunit is likely to have significant functional consequences. GABAA receptor α4 subunit expression measured by immunohistochemical labeling in brain slices is sparse across most brain regions except the thalamus, dentate gyrus, and striatum (Bencsits et al. 1999; Chandra et al. 2006; Pirker et al. 2000). However, selective modulation of α4 subunit expression in the hippocampus, using antisense oligonucleotides, has been shown to significantly alter