In contrast, a single administration of TrkB antagonist ANA-12 (0.5 mg/kg)45, 46, 47, 48, 49 did not affect depression-like phenotype in Nrf2 KO mice (Fig. 4c), suggesting a role of TrkB signaling in the PFC and hippocampus for depression-like phenotype. This evidence concerns the gene NFE2L2 and major depressive disorder.