Reduced orexin-A/OX1R mRNA expression and protein content were observed in the lateral hypothalamic region of a rat model of depression (50), and the chronic unpredictable mild stress (CUMS) model of depression reduced OXR2 expression in the ventral hippocampus, thalamus, as well as hypothalamus of rats (51). This evidence concerns the gene HCRTR2 and major depressive disorder.