Chronic activation of estrogen receptor α and β produces opposite effects on anxiety- and fear-related behaviors in female mice.

Anxiety and fear can impair daily functioning when excessive, and women are more vulnerable to anxiety- and depression-related disorders than men. Estrogens are known to influence emotion-related behaviors, but the underlying mechanisms remain unclear. Previous studies demonstrated that chronic administration of high-dose estradiol benzoate (EB) has been shown to alter emotional behaviors in female mice. In the present study, we investigated the roles of the estrogen receptor (ER) subtypes ERα and ERβ in the behavioral effects of EB using selective agonists for each receptor. Continuous treatment with the selective ERα agonist propylpyrazole triol for 2 weeks increased anxiety- and fear-related behaviors in ovariectomized female mice in the elevated zero maze and fear conditioning tests, producing effects comparable to those of high-dose EB. In contrast, treatment with the ERβ agonist diarylpropionitrile reduced these emotion-related behaviors. These findings suggest that selective activation of ERα is sufficient to reproduce the behavioral effects induced by chronic high-dose EB treatment, whereas selective activation of ERβ produces opposing effects.