Elsevier

Alcohol

Volume 41, Issue 3, May 2007, Pages 139-143
Alcohol

Editorial
Tonic for what ails us? high-affinity GABAA receptors and alcohol

https://doi.org/10.1016/j.alcohol.2007.03.008Get rights and content

Abstract

Ethanol interactions with gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, play key roles in acute intoxication. However, the exact mechanisms of these ethanol interactions have been the subject of considerable confusion and controversy. Many studies suggest that ethanol potentiates the function of the type A GABA receptor (GABAA-R). However, these findings have not been consistently replicated in experiments that directly examined the effects of ethanol on GABAA-R–mediated ion current. Differences in ethanol sensitivity of different GABAA-R subtypes have been invoked as a potential explanation for the inconsistent findings, and recent work suggests that GABAA-Rs that contain the δ subunit and/or mediate tonic extrasynaptic GABA responses may be especially ethanol sensitive. However, considerable disagreement has arisen over these findings. This special issue of Alcohol contains articles from eight research groups that are examining this issue. The authors present their work, their views on the present state of this area of alcohol research, and their ideas about how to proceed with future studies that may help to address the present confusion and controversy. This editorial provides an introduction to this line of research and the current findings and controversies.

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      Receptors containing the δ subunit, α4β3δ and α6β3δ, are more sensitive to alcohol than are γ-containing GABAA receptors [50]. However, some controversy exists over the alcohol-sensitivity of δ subunit-containing GABAA receptors and the direct action of alcohol at extrasynaptic sites [51,52]. Similarly to other ligand-gated receptors, the alcohol sensitivity of GABAA receptors is subject to modulation by intracellular signaling molecules.

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