
@article{ref1,
title="Binge alcohol drinking is associated with GABAA α2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdala",
journal="Proceedings of the National Academy of Sciences of the United States of America",
year="2011",
author="Liu, Juan and Yang, Andrew R. S. T. and Kelly, Timothy and Puche, Adam and Esoga, Chioma and June, Harry L. and Elnabawi, Ahmed and Merchenthaler, Istvan and Sieghart, Werner and June, Harry L. and Aurelian, Laure",
volume="108",
number="11",
pages="4465-4470",
abstract="Binge drinking (blood-alcohol levels ≥ 0.08 g% in a 2-h period), is a significant public health burden in need of improved treatment. Gene therapy may offer beneficial alternatives to current psychosocial and pharmacotherapeutic interventions, but identification of the target genes is a clinical challenge. We report that a GABA(A) α2 siRNA vector (pHSVsiLA2) infused into the central nucleus of the amygdala (CeA) of alcohol-preferring (P) rats caused profound and selective reduction of binge drinking associated with inhibition of α2 expression, decreased GABA(A) receptor density, and inhibition of Toll-like receptor 4 (TLR4). CeA infusion of a TLR4 siRNA vector (pHSVsiLTLR4a) also inhibited binge drinking, but neither vector functioned when infused into the ventral pallidum. Binge drinking was inhibited by a GABA(A) α1 siRNA vector (pHSVsiLA1) infused into the ventral pallidum, unrelated to TLR4. The vectors did not alter sucrose intake and a scrambled siRNA vector was negative. The data indicate that GABA(A) α2-regulated TLR4 expression in the CeA contributes to binge drinking and may be a key early neuroadaptation in excessive drinking.<p /> <p>Language: en</p>",
language="en",
issn="0027-8424",
doi="10.1073/pnas.1019020108",
url="http://dx.doi.org/10.1073/pnas.1019020108"
}