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. Author manuscript; available in PMC: 2014 Apr 21.
Published in final edited form as: Pharmacol Ther. 2010 May 11;127(3):271–282. doi: 10.1016/j.pharmthera.2010.04.003

Figure 2. Sigma receptors modulate numerous pathways implicated in the etiology or pathophysiology of depression.

Figure 2

It is believed that Ca2+ modulation through sigma receptors can act upon pathways involved in neurite outgrowth, as well as gene regulation, specifically, ERK, MAPK and Akt pathways. It is hypothesized that sigma receptor-mediated modulation of IP3Rs at the MAM, also contributes to an increase in ATP production from the mitochondria, which may have profound effects on signaling within the cell which have not yet been fully studied. Sigma receptors have also been shown to modulate PKA pathways; sigma agonists have been shown to modulate the phosphorylation of CREB, indicative of effects on gene transcription. Sigma receptors also have known effects on the transmission of signaling via neurotransmitters; however these pathways have not been fully elucidated. Dashed lines indicate known and hypothesized effects of sigma receptors on signaling pathways believed to be involved in depression.