When FoxO1 knockout mice were subjected to the FST, somewhat unexpectedly, both heterozygous and homozygous FoxO1 knockout male mice displayed prolonged immobility in the FST when compared to wild-type controls (Figure 4c), suggesting an increase in depressive behavior in mice lacking brain FoxO1. Similarly, a prolonged immobility was also observed in female homozygous FoxO1 knockout mice. To confirm the depressive behavior in FoxO1 knockout mice, another group of male wild-type and homozygous FoxO1 knockout mice were tested in the TST. Homozygous FoxO1 knockout mice again displayed prolonged immobility (Figure 4d), confirming the depressive phenotype of these mice. The increased immobility time in brain FoxO1 knockout mice was unlikely a result of impaired locomotor activity since FoxO1 knockout mice and wild-type controls had similar travel distance and velocity in the baseline Open Field Test (OFT) (Figure 4e). When the locomotor response of mice to d-amphetamine treatment (4 mg/kg, i.p., 30 min) was tested, the travel distance and velocity in wild-type and FoxO1 knockout mice were increased by 348.23±47.21% and 275.04±43.19%, respectively. Although FoxO1 knockout mice showed a trend towards slightly lower response to d-amphetamine, the difference was not significant.
