Repeated administration of METH leads to a marked increase in BDNF–TrkB signaling in the nucleus accumbens shell, eventually resulting in the long-lasting depression-like behavior that was observed in mice after METH withdrawal (Berton et al., 2006; Zhang et al., 2014; Wook Koo et al., 2016; Qiao et al., 2017). This evidence concerns the gene BDNF and depressive disorder.