Enhanced expression of brain interferon-alpha and serotonin transporter in immunologically induced fatigue in rats

Eur J Neurosci. 2005 Dec;22(11):2817-26. doi: 10.1111/j.1460-9568.2005.04478.x.


Immunologically induced fatigue was induced in rats by intraperitoneal injection of a synthetic double-stranded RNA, polyriboinosinic : polyribocytidylic acid (poly I:C). An injection of poly I:C (3 mg/kg) decreased the daily amounts of spontaneous running wheel activity to approximately 60% of the preinjection level until day 8. Quantitative analysis of mRNA levels demonstrated that interferon-alpha (IFN-alpha) and p38 mitogen-activated protein kinase mRNAs increased in the medial preoptic, paraventricular and ventromedial hypothalamic nuclei and in cortex on both days 1 and 8, while interleukin-1beta and an inhibitor of nuclear factor kappaB (IkappaB)-beta mRNAs increased on day 1, but recovered within a week. Serotonin transporter (5-HTT) mRNA also increased on days 1 and 8 after poly I:C injection in the same brain regions where IFN-alpha mRNA increased. The increased 5-HTT had a functional significance, because in vivo brain microdialysis revealed that an i.p. injection of poly I:C induced a decrease in the extracellular concentration of 5-HT in the prefrontal cortex; the decrease was blocked by local perfusion with a nonselective 5-HT reuptake inhibitor, imipramine. Finally, the poly I:C-induced fatigue was attenuated by a 5-HT1A receptor agonist but not by 5-HT2, 5-HT3 or dopamine D3 agonists. These findings, taken together, suggest that disorders in brain IFN-alpha and 5-HTT expression may be involved in the neuronal mechanisms of the poly I:C-induced fatigue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain Chemistry / immunology
  • Brain Chemistry / physiology*
  • Cytokines / biosynthesis
  • Dopamine Agonists / pharmacology
  • Fatigue / immunology*
  • Fatigue / metabolism*
  • I-kappa B Proteins / biosynthesis
  • Interferon Inducers / pharmacology
  • Interferon-alpha / biosynthesis*
  • Interleukin-1 / biosynthesis
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Poly I-C / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Serotonin Plasma Membrane Transport Proteins / biosynthesis*
  • Serotonin Receptor Agonists / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Cytokines
  • Dopamine Agonists
  • I-kappa B Proteins
  • Interferon Inducers
  • Interferon-alpha
  • Interleukin-1
  • RNA, Messenger
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists
  • p38 Mitogen-Activated Protein Kinases
  • Poly I-C