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 GABAA 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 GABAA 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 GABAA 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 GABAA α2-regulated TLR4 expression in the CeA contributes to binge drinking and may be a key early neuroadaptation in excessive drinking.
Read Full Abstract
Request Reprint E-Mail: laurelia@umaryland.edu