GPR26 -deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala

Abstract Anxiety disorders are among the most common and well studied psychiatric disorders in humans. A number of animal models have been established to study the mechanisms of anxiety and to test putative anxiolytic drugs. Gpr26 belongs to the G-protein-coupled receptor family and is exclusively expressed in brain tissue. To investigate the biological function of Gpr26 in vivo , we have generated Gpr26 knockout mice. The mutant mice grew and developed normally but displayed increased levels of anxiety-like behaviors in the open field and elevated plus maze tests, as well as a higher level of depression-like behaviors in the forced-swim and tail-suspension tests. Meanwhile, no significant alteration in spatial learning and memory abilities were found for Gpr26 -deficient mice in the Morris water maze test. Previous studies demonstrated that lower protein kinase A (PKA)–cAMP responsive element-binding protein (CREB)–neuropeptide Y (NPY) signaling in the amygdala is linked to higher anxiety and excessive alcohol-drinking behaviors in rats. Therefore, we further examined the phosphorylated CREB (pCREB) and CREB levels in the brains of Gpr26 -deficient mice. Reduced pCREB levels were observed in the central amygdala but not in the other regions, while total CREB levels remained comparable between wild-type and mutant mice. Combined, our data indicate that Gpr26 is important for emotion regulation in mice, a function probably mediated by the phosphorylation of CREB in the central amygdala.