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GAL 3 receptor knockout mice exhibit an alcohol‐preferring phenotype
Author(s) -
Genders Shannyn G.,
Scheller Karlene J.,
Jaehne Emily J.,
Turner Bradley J.,
Lawrence Andrew J.,
Brunner Susanne M.,
Kofler Barbara,
Buuse Maarten,
Djouma Elvan
Publication year - 2019
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12641
Subject(s) - saccharin , endocrinology , medicine , knockout mouse , ethanol , alcohol , receptor , neuropeptide , galanin , antagonist , alcohol use disorder , agonist , chemistry , psychology , biology , biochemistry
Abstract 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.