TY  - JOUR
PY  - 2011//
TI  - Binge alcohol drinking is associated with GABAA α2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdala
JO  - Proceedings of the National Academy of Sciences of the United States of America
A1  - Liu, Juan
A1  - Yang, Andrew R. S. T.
A1  - Kelly, Timothy
A1  - Puche, Adam
A1  - Esoga, Chioma
A1  - June, Harry L.
A1  - Elnabawi, Ahmed
A1  - Merchenthaler, Istvan
A1  - Sieghart, Werner
A1  - June, Harry L.
A1  - Aurelian, Laure
SP  - 4465
EP  - 4470
VL  - 108
IS  - 11
N2  - 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>
LA  - en
SN  - 0027-8424
UR  - http://dx.doi.org/10.1073/pnas.1019020108
ID  - ref1
ER  -