Since chronic stress elevated circulating ghrelin, and ghrelin/GHS-R1a signaling shares a majority of downstream molecular pathways involved in the pathophysiology of depression, we checked the activation of multiple signaling pathways in the hippocampus of GHS-R1a knock-out mice and their wild-type littermates exposure to CSDS, including activity of Akt, ERK1/2, JNK, CREB, and p38 MAPK. This evidence concerns the gene MAPK3 and major depressive disorder.