Basis of the gabamimetic profile of ethanol.
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 GABA(A) receptors containing the delta subunit display sensitivity to low intoxicating ethanol concentrations and this sensitivity is further increased by a mutation in the cerebellar alpha6 subunit, found in alcohol-hypersensitive rats. Dr. Mameli reported that ethanol affects gamma-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 GABA(A) receptors.
Bowles Center for Alcohol Studies, UNC School of Medicine, Chapel Hill, North Carolina 27599, USA. george_breese@med.unc.edu
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Breese
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Criswell
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Carta
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Dodson
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Hanchar
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Khisti
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Mameli
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Ming
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Morrow
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Olsen
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Otis
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Parsons
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Penland
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Roberto
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Siggins
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D000437:Alcoholism / Q000235:genetics; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000737:chemistry; D000431:Ethanol / Q000494:pharmacology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D017354:Point Mutation; D011374:Progesterone / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D013256:Steroids / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D000777:Anesthetics; D011963:Receptors, GABA-A; D013256:Steroids; D000431:Ethanol; D011374:Progesterone; D005680:gamma-Aminobutyric Acid