GAL3 receptor KO mice exhibit an anxiety-like phenotype

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems. It is a modulator of various physiological and pathological processes, and it mediates its effects via three G protein-coupled receptors (GAL(1-3) receptors). A role for GAL as a modulator of mood and anxiety was suggested, because GAL and its receptors are highly expressed in limbic brain structures of rodents. In recent years, numerous studies of animal models have suggested an involvement of GAL and GAL(1) and GAL(2) receptors in anxiety-and depression-related behavior. However, to date, there is sparse literature implicating GAL(3) receptors in behavioral functions. Therefore, we studied the behavior of GAL(3) receptor-deficient (GAL(3)-KO) mice to elucidate whether GAL(3) receptors are involved in mediating behavior-associated actions of GAL. The GAL(3)-KO mouse line exhibited normal breeding and physical development. In addition to behavioral tests, phenotypic characterization included analysis of hematology, amino acid profiles, metabolism, and sudomotor function. In contrast to WT littermates, male GAL(3)-KO mice exhibited an anxiety-like phenotype in the elevated plus maze, open field, and light/dark box tests, and they were less socially affiliated than WT animals to a stranger mouse in a social interaction test. In conclusion, our data suggest involvement of GAL(3) receptors in GAL-mediated effects on mood, anxiety, and behavior, making it a possible target for alternative treatment strategies for mood disorders.