The complex role of the serotonin transporter in adult neurogenesis and neuroplasticity. A critical review

Objectives. Studies on the serotonin transporter (SERT) with regard to neurogenesis and neuroplastic effects on the adult brain are scarce. This is intriguing since neurogenesis is believed to play a decisive role in modulating the effect of selective serotonin reuptake inhibitors (SSRI), which are targeting SERT. Methods. Therefore, we reviewed the current scientific literature about the influence of serotonin on neurogenesis with particular emphasis on SERT in various settings, both in vivo and in vitro. Results. Experiments using SERT KO (knock-out) animal models showed that SERT does not directly or indirectly influence neurogenesis in vitro, whereas compensatory mechanism seem to participate in vivo. Conclusion. At least with regard to adult neural stem cells, the impact of serotonin (5-HT) on neuroplasticity and neurogenesis is not due to SERT-mediated effcts. Instead, serotonergic fine-tuning may be exerted by a number of other different mechanisms including endogenous production of 5-HT in adult neural stem cells, uptake of 5-HT into adult neural stem cells by other monoamine transporters, and actions of the 5-HT1A receptors present on these cells.