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.