CRHR1 and major depressive disorder: Additionally, another study has posited that elevated phosphorylation of hippocampal ERK1/2, mediated through enhanced activation of CRF1, may contribute to the depression-like behaviors observed in CRF2−/− mice (Todorovic et al., 2009), which suggesting that ERK1/2 may serve as a critical target for investigating the neuronal mechanisms underlying stress-induced affective disorders (Tronson et al., 2008).