Abstract
We have recently found that an intraperitoneal (i.p.) injection of a synthetic double-stranded RNA, polyriboinosinic: polyribocytidylic acid (poly I:C), which mimics viral infection, induces interferon-α (IFN-α) and serotonin (5-HT) transporter (5-HTT) in the brain. To explore the functional significance of their expression, we determined extracellular concentrations of 5-HT and other monoamines such as noradrenaline (NA) and dopamine (DA) in the medial prefrontal cortex (mPFC) of freely moving rats using in vivo microdialysis method. Following an i.p. injection of poly I:C (3 mg/kg), NE levels in the mPFC transiently increased but returned to the basal level within 6 hrs after the injection. DA levels were not affected by poly I:C. On the other hand, 5-HT concentration in the mPFC decreased to 60-70% of the basal level until 8 hrs after poly I:C, while levels of a 5-HT metabolite, 5-hydroxyindole acetic acid, did not alter. The poly I:C-induced decrease in 5-HT was significantly attenuated by local perfusion with a selective 5-HT reuptake inhibitor (fluoxetine) in the mPFC. Microinjection of IFN-α into the mPFC also decreased 5-HT levels, which was again attenuated by perfusion with fluoxetine. It is considered that the poly I:C-induced 5-HTT, which is shown to be induced by IFN-α in astrocytes or endothelial cells, may scavenge extracellular 5-HT into the blood or cerebrospinal fluid, thereby decreasing 5-HT levels. We have reported that the decrease in 5-HT in the brain is closely related to the central mechanisms of fatigue. [J Physiol Sci. 2006;56 Suppl:S104]
