Basis of the gabamimetic profile of ethanol

G. R. Breese, H. E. Criswell, M. Carta, P. D. Dodson, H. J. Hanchar, R. T. Khisti, M. Mameli, Z. Ming, A. L. Morrow, R. W. Olsen, T. S. Otis, L. H. Parsons, S. N. Penland, M. Roberto, G. R. Siggins, C. F. Valenzuela, M. Wallner
Alcoholism Clin Exp Res. 2006-04-01; 30(4): 731-744
DOI: 10.1111/j.0145-6008.2006.00086.x

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1. Alcohol Clin Exp Res. 2006 Apr;30(4):731-44.

Basis of the gabamimetic profile of ethanol.

Breese GR(1), Criswell HE, Carta M, Dodson PD, Hanchar HJ, Khisti RT, Mameli M,
Ming Z, Morrow AL, Olsen RW, Otis TS, Parsons LH, Penland SN, Roberto M, Siggins
GR, Valenzuela CF, Wallner M.

Author information:
(1)Bowles Center for Alcohol Studies, UNC School of Medicine, Chapel Hill, North
Carolina 27599, USA.

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.

DOI: 10.1111/j.0145-6008.2006.00086.x
PMCID: PMC2958095
PMID: 16573592 [Indexed for MEDLINE]

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