Binge alcohol drinking is associated with GABAA alpha2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdala.
paper
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- Authors
- Liu, Juan; Yang, Andrew R; Kelly, Timothy; Puche, Adam; Esoga, Chioma; June, Harry L; Elnabawi, Ahmed; Merchenthaler, Istvan; Sieghart, Werner; June, Harry L; Aurelian, Laure
- Year
- 2011
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 21368176
- DOI
- 10.1073/pnas.1019020108
- PMCID
- PMC3060224
Binge drinking (blood-alcohol levels β₯ 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) Ξ±2 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 Ξ±2 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) Ξ±1 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) Ξ±2-regulated TLR4 expression in the CeA contributes to binge drinking and may be a key early neuroadaptation in excessive drinking.
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