Considering the role of BDNF–TrkB signaling in the NAc in depression,16, 30, 33, 44, 45, 46 our findings suggest that a marked increase of BDNF within the NAc by repeated METH exposure contributes to long-lasting behavioral abnormalities (depression and behavioral sensitization) and that TrkB antagonists confer beneficial effects against these behavioral abnormalities by blocking TrkB signaling in the NAc shell, but not NAc core. Here, BDNF is linked to major depressive disorder.