Therefore, we conducted an animal experiment to explore the antidepressant effects of three taVNS frequencies (5, 20, and 100 Hz) by comparing behavioral changes (assessed by sucrose water preference rate, forced swimming immobility time, and open-field movement score) and function of hypothalamus-pituitary-adrenal (HPA) axis [assessed by plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) concentrations] of chronic unpredictable mild stress (CUMS) depression model rats. The gene discussed is POMC; the disease is major depressive disorder.