N-Acetyl-5-hydroxytryptamine is a Melatonin precursor, and that it can potently activate TrkB receptor. IC50 & Target: TrkB receptor^[1] In Vitro: N-Acetyl-5-hydroxytryptamine (NAS), a precursor of Melatonin, is acetylated from serotonin by AANAT (arylalkylamine N-acetyltransferase). N-acetylserotonin activates TrkB receptor in a circadian rhythm. N-Acetyl-5-hydroxytryptamine swiftly activates TrkB in a circadian manner and exhibits antidepressant effect in a TrkB-dependent manner. N-Acetyl-5-hydroxytryptamine rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin- and MT3 receptor-independent manner^[1]. In Vivo: To explore whether N-Acetyl-5-hydroxytryptamine, can trigger TrkB activation in vivo, TrkB F616A knockin mice are employed, where it has been shown that TrkB F616A activation can be selectively blocked by 1NMPP1, a derivative of kinase inhibitor PP1, leading to TrkB-null phenotypes. To assess whether N-Acetyl-5-hydroxytryptamine can mimic BDNF, cortical neurons from TrkB F616A knockin mice are prepared. In alignment with a previous report, BDNF- and NAS-mediated TrkB phosphorylation are selectively reduced by 1NMPP1 but not by K252a, whereas serotonin or Melatonin had no effect . These findings suggest that NAS strongly provokes both wild-type TrkB and TrkB F616A tyrosine phosphorylation and activation^[1].