CRHR1 and major depressive disorder: The activation of CRF1 by the intracerebroventricular (ICV) injection of CRF and Ucn1 evokes the activation of the HPA axis, as well as anxiety-like and depression-like behavior [2,17,18], whereas activation of CRF2 by the ICV administration of Ucn2 and Ucn3 has anxiolytic and antidepressant effects in rats [19,20,21,22].