title: 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.
authors.affiliation: Laboratory of Genetic Engineering, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Zhang
authors.forename: J-J
authors.initials: JJ
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: X-B
authors.initials: XB
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Kuang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Wan
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: H-M
authors.initials: HM
authors.lastname: Yan
authors.forename: J
authors.initials: J
authors.lastname: Fei
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology; D000679:Amygdala / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003863:Depression / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C520707:G protein-coupled receptor GPR26, mouse; D043562:Receptors, G-Protein-Coupled