To test if the low expression of FoxO3a in FoxO3a-deficient mouse brain contributes to the antidepressant phenotype, we measured the levels of cytosolic and nuclear FoxO3a after wild type mice were treated with the antidepressant imipramine (20 mg/kg/day, i.p.) for 28 days. Comparing to saline-treated wild-type mice, an increase in the level of cytosolic FoxO3a and a corresponding decrease in the level of nuclear FoxO3a was noticeable in the cerebral cortex of mice treated with imipramine (Figure 5d), therefore suggesting that the lowered level of FoxO3a may contribute to the antidepressant behavior.