title: GPER1 (GPR30) knockout mice display reduced anxiety and altered stress response in a sex and paradigm dependent manner.
abstract: The putative estrogen receptor GPER1 (the former orphan receptor GPR30) is discussed to be involved in emotional and cognitive functions and stress control. We recently described the induction of anxiety-like effects by the GPER1 agonist G-1 upon systemic injection into mice. To contribute to a better understanding of the role of GPER1 in anxiety and stress, we investigated germ-line GPER1 deficient mice. Our experiments revealed marked differences between the sexes. A mild but consistent phenotype of increased exploratory drive was observed in the home cage, the elevated plus maze and the light-dark choice test in male GPER1 KO mice. In contrast, female GPER1-KO mice displayed a less pronounced phenotype in these tests. Estrous-stage dependent mild anxiolytic-like effects were observed solely in the open field test. Notably, we observed a strong shift in acute stress coping behavior in the tail suspension test and basal corticosterone levels in different phases of the estrous cycle in female GPER1-KO mice. Our data, in line with previous reports, suggest that GPER1 is involved in anxiety and stress control. Surprisingly, its effects appear to be stronger in male than female mice.
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, A-6020 Innsbruck, Austria.
authors.forename: Iris
authors.initials: I
authors.lastname: Kastenberger
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1a, A-6020 Innsbruck, Austria. Electronic address: schwarzer.christoph@i-med.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwarzer
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000235:genetics*
chemical_list: C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D003345:Corticosterone
keywords: Anxiety; Corticosterone; Emotional control; Estrous cycle; G-protein coupled estrogen receptor; Stress coping