In conclusion, our study demonstrated that an increased BDNF–TrkB signaling in the NAc shell may be implicated in the long-lasting behavioral abnormalities (depression and behavioral sensitization) in mice after the repeated exposure to METH and that blockage of TrkB signaling by ANA-12 could attenuate these behavioral abnormalities after METH withdrawal. Here, NTRK2 is linked to major depressive disorder.