Proneurogenic Effects of Trazodone in Murine and Human Neural Progenitor Cells

Several antidepressants increase adult hippocampal neurogenesis (ahNG) in rodents, primates, and, potentially, humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of murine adult hippocampal neural progenitor cells (ahNPCs) and human induced pluripotent stem cell (iPSC)-derived NPCs. We demonstrated that TZD enhances neuronal differentiation of murine as well as human NPCs. TZD is a multimodal antidepressant, which binds with high affinity to 5-HT2a, α1, and 5-HT1a and with lower affinity to 5-HT2c, α2 and 5-HTT. We demonstrated that TZD proneurogenic effects were mediated b...