Previous research has repeatedly demonstrated an important role for ERβ activation in reducing anxiety-and depression-like behaviors in OVX mice and rats (Frye and Walf, 2004; Lagunas et al., 2010; Li et al., 2014; Lund et al., 2005; Oyola et al., 2012; Rocha et al., 2005; Walf et al., 2004, Walf and Frye, 2005a, 2007). The gene discussed is ESR2; the disease is major depressive disorder.