HRH3 and major depressive disorder: Rodent studies revealed that acute and chronic treatment with an H3R antagonist can reduce depression-like conditions and that chronic H3R antagonism (via ciproxifan) alleviates depression-like conditions in mice via the modulation of stress-induced biochemical correlates such as BDNF, corticosterone, NUCB2/nesfatin-1, and CRH in the brain (51, 76, 77).