The effects of 5-hydroxytryptamine (5-HT) on several types of neuronal inju
ry in mouse cortical cell cultures were tested. Co-treatment with 5-HT prev
ented free radical-mediated neuronal necrosis induced by FeCl2 or buthionin
e sulfoximine (BSO) in a dose-dependent manner. Subtype antagonists did not
reverse the protective effect and 5-HT showed direct free radical scavengi
ng activity evidenced by its ability to reduce the stable free radical 1,1-
diphenyl-2-picrylhydrazyl (DPPH) in a cell-free system. Excitotoxic necrosi
s induced by NMDA or apoptosis induced by staurosporine was not sensitive t
o 5-HT treatment. These features raise the possibility that the endogenous
neurotransmitter 5-HT may work as an innate antioxidant defense mechanism i
n the CNS. NeuroReport 12:963-966 (C) 2001 Lippincott Williams & Wilkins.