Two structurally distinct GLO1 inhibitors (S-bromobenzylglutathione cyclopentyl diester or methyl-gerfelin) ameliorated depression-like behavior in a rodent model after 5 days of treatment, whereas an existing antidepressant, fluoxetine, takes 14 days of treatment to ameliorate depression-like behavior. Here, GLO1 is linked to major depressive disorder.