In the present study, we firstly observed the effects of chronic GTS treatment on depression-like behavior and some hippocampal plasticity-related proteins in male C57BL/6N mice, then investigated the aforementioned effects in the corticosterone-induced mouse depression model, and explored the underlying mechanism with respect to the GSK-3β-CREB signaling pathway. This evidence concerns the gene CREB1 and major depressive disorder.