Binge alcohol drinking is associated with GABAA alpha2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdala

Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4465-70. doi: 10.1073/pnas.1019020108. Epub 2011 Feb 28.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / metabolism*
  • Amygdala / metabolism*
  • Amygdala / pathology
  • Animals
  • Genetic Vectors
  • Humans
  • RNA, Small Interfering / metabolism
  • Rats
  • Receptors, GABA-A / metabolism*
  • Toll-Like Receptor 4 / metabolism*


  • Gabra2 protein, rat
  • RNA, Small Interfering
  • Receptors, GABA-A
  • Tlr4 protein, rat
  • Toll-Like Receptor 4