CRH and major depressive disorder: Early observations in rodents also found that intracerebroventricular (ICV) administration of CRF induced anxiety and depression-like behaviors, whereas the injection of CRF antagonists produced the opposite effect, confirming the potential antidepressive properties of CRF ligands (Deak et al., 1999; Zobel et al., 2000; Seymour et al., 2003).