Possible involvement of brain cytokines and 5-HT system in chronic fatigue syndrome

We have recently developed an animal model for fatigue induced by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs, polyriboinosinic:polyribocytidylic acid (poly I:C) in rats. This animal model shows a decrease in daily amounts of spontaneous running wheel activity to about 60% of the preinjection level, and increase in interferon-α (IFN-α) mRNA in rat hypothalamic nuclei and cortex for more than a week. In addition, serotonin transporter (5-HTT), which is induced by IFN-α, also increased in the same regions. In vivo brain microdialysis demonstrated a decrease in 5-HT levels in the prefrontal cortex after poly I:C, which was blocked by a selective 5-HT reuptake inhibitor, fluoxetine. Furthermore, the poly I:C-induced suppression of the running wheel activity was attenuated by a 5-HT1A receptor agonist, but not by 5-HT2 and 5-HT3 receptor agonists. Possible involvement of IFN-α and 5-HT system in the mechanisms of the poly I:C-induced fatigue as well as CFS was discussed.