Abstract
The immunologically induced fatigue was conducted in rats by intraperitoneal (IP) injection of a synthetic double-stranded RNAs, poly I:C. An IP injection of poly I:C (3 mg/kg) induced fever and a decrease in spontaneous activity. In vivo brain microdialysis revealed that the extracellular concentration of 5-HT in the prefrontal cortex (PFC) decreased after poly I:C injection, which was blocked by selective 5-HT reuptake inhibitor (SSRI), fluoxetine. The amount of mRNA for interferon-α (IFN-α), as well as serotonin transporter (5-HTT) mRNA, which is known to be induced by IFN-α in astrocytes, increased in the PFC. Microinjection of IFN-α decreased the 5-HT concentration, which was also blocked by SSRI. Furthermore, the poly I:C-induced suppression of activity was attenuated by 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) or SSRI. These findings, taken together, suggest that brain IFN-α and 5-HT system play an important role in the neuronal mechanisms of the immunologically induced fatigue by poly I:C.
To further investigate the central mechanisms of fatigue, we tried to make a conditioning model of immunologically induced fatigue. After habituating rats to restricted drinking (30 min a day), saccharin water was given just before the injection of polyI:C (1 mg/kg) only on the day of conditioning. When saccharin water was given again four days later, fever and reduction of spontaneous activity were observed. We further tried to investigate the central mechanisms of fatigue using this conditioned fatigue model. [Jpn J Physiol 54 Suppl:S235 (2004)]
