Given its therapeutic potential and the crucial roles of brain‐derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and the GluN2B subunit of the N‐methyl‐D‐aspartate (NMDA) receptor in the pathophysiology and treatment of depression, this study aimed to evaluate the effects of Riparin A on the expression of these neurotrophic factors and receptor subunit in the hippocampus and cortex of rats subjected to the chronic unpredictable mild stress (CUMS) model of depression. The gene discussed is GRIN2B; the disease is major depressive disorder.