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Basis of the Gabamimetic Profile of Ethanol


  • This work was supported by NIH grants to TSO (NS41651), to CFV (AA 014973), to GRB (AA12655 and AA11605), to RWO (NS35985 and AA07680), to MR, GRS, and LHP (AA013517, AA06420, and AA014619), and to ALM (AA10564 and AA13515). Additional support came from a NIH predoctoral fellowship to HJH (AA015460), an Alcoholic Beverage Medical Research Foundation grant to MW, a Human Frontiers Science Program Fellowship award to PDD, and medical research award on alcohol and substance abuse through the UCSF to RWO from the State of California.

Reprint requests: G. R. Breese, Bowles Center for Alcohol Studies, UNC School of Medicine, Chapel Hill, NC 27599; Fax: 919-966-5679; E-mail:


This article summarizes the proceedings of a symposium held at the 2005 Research Society on Alcoholism meeting. The initial presentation by Dr. Wallner provided evidence that selected GABAA receptors containing the δ subunit display sensitivity to low intoxicating ethanol concentrations and this sensitivity is further increased by a mutation in the cerebellar α6 subunit, found in alcohol-hypersensitive rats. Dr. Mameli reported that ethanol affects γ-aminobutyric acid (GABA) function by affecting neural circuits that influence GABA release. Dr. Parsons presented data from electrophysiological and microdialysis investigations that ethanol is capable of releasing GABA from presynaptic terminals. Dr. Morrow demonstrated that systemic ethanol increases neuroactive steroids in brain, the absence of which alters various functional responses to ethanol. Dr. Criswell presented evidence that the ability of ethanol to increase GABA was apparent in some, but not all, brain regions indicative of regional specificity. Further, Dr. Criswell demonstrated that neurosteroids alone and when synthesized locally by ethanol act postsynaptically to enhance the effect of GABA released by ethanol in a region specific manner. Collectively, this series of reports support the GABAmimetic profile of acutely administered ethanol being dependent on several specific mechanisms distinct from a direct effect on the major synaptic isoforms of GABAA receptors.