Conditional mutagenesis of CRFR1 using a Cre-Lox system has led to the development of various conditional knockouts were CRFR1 has been deleted in specific neuron populations previously implicated in stress and stress-associated anxiety and depression: (a) CRFR1GLU-CKO, where CRFR1 is deleted in forebrain glutamatergic neurons; (b) CRFR1GABA-CKO, deleting the receptor in forebrain GABAergic neurons; (c) CRFR1DA-CKO, carrying CRFR1 deletion in midbrain dopaminergic neurons; and (d) CRFR15HT-CKO, deleting CRFR1 in brainstem serotonergic neurons (Refojo et al., 2011) (Figure 2). This evidence concerns the gene CRHR1 and major depressive disorder.