Based on AKT, MAPK and mTOR signaling pathways, 11 key proteins (AKT/p-AKT, ERK12/p-ERK12, GluA-1, mTOR/p-mTOR, MEK1/p-MEK1, MEK2/p-MEK2, P38/p-P38, P70S6K/ p-P70S6K, PSD95, Syn1 and TrkB) were chosen to be validated by western blot in four depression models. This evidence concerns the gene MAP2K2 and major depressive disorder.