Although ERβ agonism has been reported to lower anxiety-related phenotypes in mice and rats (Rocha et al., 2005; Walf and Frye, 2005; Walf and Frye, 2007), other studies report no effects of ERβ agonism on anxiety- and depression-like behaviors in female mice (Eid et al., 2020). Here, ESR2 is linked to major depressive disorder.