Stimulation of the sigma-1 receptor and the effects on neurogenesis and depressive behaviors in mice

Sigma-1 receptor (Sig-1R) is molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to mitochondria. Recent studies show that Sig-1R stimulation antagonizes depressive-like behaviors in animal models, but molecular mechanisms underlying this effect remain unclear. Here, we focus on the effects of Sig-1R ligands on hippocampal neurogenesis and depressive-like behaviors. Sig-1R stimulation also enhances CaMKII/CaMKIV and protein kinase B (Akt) activities in hippocampus. Therefore, we discuss the fundamental roles of Sig-1R, CaMKII/CaMKIV and protein kinase B (Akt) signaling in amelioration of depressive-like behaviors following Sig-1R stimulation.