Significant changes in GR and 5-HT2AR expression in the PFC, amygdala and hippocampus were induced by OD in rats, with or without CUS, and the more obvious alterations observed in the OD + CUS group may indicate that OD may be a promoting factor for depression through the hypothalamus–pituitary–adrenal (HPA) axis and 5-HT system. This evidence concerns the gene NR3C1 and major depressive disorder.