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Enhanced expression of brain interferon‐α and serotonin transporter in immunologically induced fatigue in rats
Author(s) -
Katafuchi Toshihiko,
Kondo Tetsuya,
Take Sachiko,
Yoshimura Megumu
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04478.x
Subject(s) - serotonin transporter , microdialysis , serotonin , medicine , endocrinology , intraperitoneal injection , agonist , chemistry , dopamine , extracellular , prefrontal cortex , reuptake , 5 ht receptor , receptor , pharmacology , biology , neuroscience , biochemistry , cognition
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 ≈ 60% of the preinjection level until day 8. Quantitative analysis of mRNA levels demonstrated that interferon‐α (IFN‐α) 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‐1β and an inhibitor of nuclear factor κB (IκB)‐β 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‐α 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‐HT 1A receptor agonist but not by 5‐HT 2 , 5‐HT 3 or dopamine D 3 agonists. These findings, taken together, suggest that disorders in brain IFN‐α and 5‐HTT expression may be involved in the neuronal mechanisms of the poly I:C‐induced fatigue.