Lack of functional estrogen receptor β influences anxiety behavior and serotonin content in female mice

Estrogen has been linked to the modulation of anxiety in females. Here we report results of anxiety tests conducted in female estrogen receptor β (ERβ) knockout (ERβKO) and wild-type (WT) mice. Ovariectomized (OVX) mice treated with chronic estradiol (E2) replacement did not behave differently on the elevated plus-maze when compared with OVX mice that did not experience hormone replacement. However, a genotype difference was noted; WT females were more likely to explore the distal portion of the open arm of the maze than ERβKO littermates. In addition, ERβKO female mice had significantly lower serotonin (5-HT) content than WT littermates in several brain regions including: the bed nucleus of the stria terminalis, preoptic area, and hippocampus. A similar trend was noted in the dorsal raphe nucleus. Dopamine content was reduced within the caudate putamen in ERβKO mice as compared to brains from WT animals. Thus, in the absence of functional ERβ, regardless of the presence or absence of circulating E2 in plasma, female mice exhibited enhanced anxiety and decreased concentrations of 5-HT or dopamine in several brain regions. We hypothesize that ERβ is required during development to modulate the effects of estrogen on anxiety and catecholamine concentrations in female mouse brains.