GAL3 receptor knockout mice exhibit an alcohol-preferring phenotype

Galanin is a neuropeptide which mediates its effects via three G-protein coupled receptors (GAL(1-3)). Administration of a GAL(3) antagonist reduces alcohol self-administration in animal models while allelic variation in the GAL(3) gene has been associated with an increased risk of alcohol use disorders in diverse human populations. Based on the association of GAL(3) with alcoholism, we sought to characterize drug-seeking behavior in GAL(3)-deficient mice for the first time. In the two-bottle free choice paradigm, GAL(3)-KO mice consistently showed a significantly increased preference for ethanol over water when compared to wildtype littermates. Furthermore, male GAL(3)-KO mice displayed significantly increased responding for ethanol under operant conditions. These differences in alcohol seeking behavior in GAL(3)-KO mice did not result from altered ethanol metabolism. In contrast to ethanol, GAL(3)-KO mice exhibited similar preference for saccharin and sucrose over water, and a similar preference for a high fat diet over a low fat diet as wildtype littermates. No differences in cognitive and locomotor behaviors were observed in GAL(3)-KO mice to account for increased alcohol seeking behavior. Overall, these findings suggest genetic ablation of GAL(3) in mice increases alcohol consumption.