A role for beta-arrestin 2 in mediating the rewarding properties of ethanol

It is widely believed that the opiate system is involved in the development of alcoholism. Beta arrestin 2 (Arrb2) is a crucial modulator of this system; suggesting that Arrb2 is important for drug reward behaviors. In this study we further elucidated the putative role of Arrb2 in ethanol consumption. We fi rst compared Arrb2 brain expression levels between alcohol-preferring AA and nonpreferring ANA rats by in situ hybridization. We found differential expression levels in ventral and dorsal striatum, as well as hippocampus. Sequence analysis of Arrb2 showed a novel haplotype variant that completely discriminates between the lines. We then characterized the impact of this gene on ethanol related behaviors using Arrb2 null-mutant mice. Compared to wild type animals, Arrb2 mutant and heterozygote mice demonstrate reduced voluntary ethanol consumption and reduced ethanol induced locomotion. Mutant mice also show a decreased sensitivity to ethanol-induced sedation. Our data support a role for Arrb2 in mediating the rewarding effects of ethanol.