Knockdown of Tlr3 in dorsal striatum reduces ethanol consumption and acute functional tolerance in male mice.

ABSTRACT: Systemic activation of toll-like receptor 3 (TLR3) signaling using poly(I:C), a TLR3 agonist, drives ethanol consumption in several rodent models, while global knockout of Tlr3 reduces drinking in C57BL/6J male mice. To determine if brain TLR3 pathways are involved in drinking behavior, we used CRISPR/Cas9 genome editing to generate a Tlr3 floxed (Tlr3^F/F) mouse line. After sequence confirmation and functional validation of Tlr3 brain transcripts, we injected Tlr3^F/F male mice with an adeno-associated virus expressing Cre recombinase (AAV5-CMV-Cre-GFP) to knockdown Tlr3 in the medial prefrontal cortex, nucleus accumbens, or dorsal striatum (DS). Only Tlr3 knockdown in the DS decreased two-bottle choice, every-other-day (2BC-EOD) ethanol consumption. DS-specific deleti

SUBMITTER: Dilly GA 

PROVIDER: S-EPMC11007683 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature