For example, in depression model rats, EA could reverse CUS induced considerable upregulation of p-ERK expression, ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB in the hippocampus [47], or enhanced the activation of hippocampal ERK signaling pathway [48], suggesting an involvement of hippocampal ERK–CREB signaling in EAS-induced antidepressant-like effects. This evidence concerns the gene MAPK3 and major depressive disorder.