Although studies have shown that Neuregulin 1 (NRG1) and it's signaling pathway are associated with depression, the possible regulatory relationship of esketamine on the NRG1-ErbB4 pathway is not yet clear.<h4>Methods</h4>To induce depressive-like behavior in mice, a Chronic Social Defeat Stress (CSDS) model was established. Here, ERBB4 is linked to major depressive disorder.