The role of GABA sub(A) receptors in the acute and chronic effects of ethanol: a decade of progress

• Published in: Psychopharmacology Vol. 205; no. 4; pp. 529 - 564
• Main Authors: Kumar, Sandeep, Porcu, Patrizia, Werner, David F, Matthews, Douglas B, Diaz-Granados, Jaime L, Helfand, Rebecca S, Morrow, ALeslie
• Format: Journal Article
• Language: English
• Published: 01.09.2009
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1562-z

The past decade has brought many advances in our understanding of GABA sub(A) receptor-mediated ethanol action in the central nervous system. We now know that specific GABA sub(A) receptor subtypes are sensitive to ethanol at doses attained during social drinking while other subtypes respond to ethanol at doses attained by severe intoxication. Furthermore, ethanol increases GABAergic neurotransmission through indirect effects, including the elevation of endogenous GABAergic neuroactive steroids, presynaptic release of GABA, and dephosphorylation of GABA sub(A) receptors promoting increases in GABA sensitivity. Ethanol's effects on intracellular signaling also influence GABAergic transmission in multiple ways that vary across brain regions and cell types. The effects of chronic ethanol administration are influenced by adaptations in GABA sub(A) receptor function, expression, trafficking, and subcellular localization that contribute to ethanol tolerance, dependence, and withdrawal hyperexcitability. Adolescents exhibit altered sensitivity to ethanol actions, the tendency for higher drinking and longer lasting GABAergic adaptations to chronic ethanol administration. The elucidation of the mechanisms that underlie adaptations to ethanol exposure are leading to a better understanding of the regulation of inhibitory transmission and new targets for therapies to support recovery from ethanol withdrawal and alcoholism.