Sertraline inhibits nerve growth factor-induced neurite outgrowth in PC12 cells via a mechanism involving the sigma-1 receptor

Abstract

The selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and sertraline show a high affinity for sigma-1 receptors. Fluvoxamine enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells via a sigma-1 receptor-mediated mechanism, which suggests that neurogenesis may be involved in the antidepressant action of fluvoxamine. However, the effects of sertraline on neurite outgrowth remain unclear. Here, we report the effects of sertraline on NGF-induced neurite outgrowth in PC12 cells. At concentrations above 0.3 μM, sertraline inhibited neurite outgrowth induced by NGF (50 ng/mL) in PC12 cells in a concentration-dependent manner. At 0.3–3 μM, sertraline inhibited NGF-induced neurite outgrowth; however, had no effect on cell viability. This suggests that at these concentrations, sertraline inhibits NGF-induced neurite outgrowth without causing cell toxicity. Because sertraline has a high affinity for the sigma-1 receptor, we investigated whether this receptor is involved in sertraline's inhibitory effect on NGF-induced neurite outgrowth. The effect was reversed by both the sigma-1 receptor agonist PRE-084 and the sigma-1 receptor antagonist NE-100. These results suggest that sertraline inhibits NGF-induced neurite outgrowth in PC12 cells by acting as an inverse agonist of the sigma-1 receptor in this system.