Our hypotheses were as follows: (1) stress may induce more depression-like behavior under high-stress intensity; (2) reward might enhance stress resilience and reduce depression-like behavior, with a more significant effect under high-stress intensity; (3) and reward may render the neural damage of stress through regulating the expression level of ECs and the mGluR5 in VTA and DRN under high-stress intensity. The gene discussed is GRM5; the disease is major depressive disorder.