Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-α mRNA in rats: a model for immunologically induced fatigue

• Published in: Neuroscience 2003-09, Vol.120 (3), p.837-845
• Main Authors: Katafuchi, T, Kondo, T, Yasaka, T, Kubo, K, Take, S, Yoshimura, M
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - blood; Animals; Behavior, Animal; Biological and medical sciences; Body Temperature; Body Weight; Brain - immunology; Catecholamines - blood; Chronic Disease; Disease Models, Animal; Exploratory Behavior; Fatigue - immunology; Fundamental and applied biological sciences. Psychology; heat exposure; Hypothalamus - immunology; IFN-α; Interferon-alpha - metabolism; Interleukin-1 - metabolism; Male; Motor Activity; open field test; Poly I-C; Rats; Rats, Wistar; real-time capillary PCR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Running; Vertebrates: body movement. Posture. Locomotion. Flight. Swimming. Physical exercise. Rest. Sports
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00365-8

Following 2 weeks acclimation to the running wheel in the home cages, an i.p. injection of a synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly I:C, 3 mg/kg), was performed to produce the immunologically induced fatigue in rats. The daily amounts of spontaneous running wheel activity decreased to about 40–60% of the preinjection level until day 9 with normal circadian rhythm, then gradually returned to the baseline level by day 14. Rats given a heat exposure (36 °C for 1 h) for the consecutive 3 days showed an increase in activity except for the first day. In the open field test, the total moving distance and the number of rearing of the poly I:C-injected rats decreased on day 1, but they were not different from the saline-injected group on day 7, suggesting that the poly I:C-induced fatigue on day 7 was not due to the peripheral problems such as muscle/joint pain, but involved the CNS. Quantitative analysis of mRNA levels using a real-time capillary reverse transcriptase-polymerase chain reaction (RT-PCR) method revealed that interferon-α (IFN-α) mRNA contents in the cortex, hippocampus, hypothalamic medial preoptic, paraventricular, and ventromedial nuclei were higher in the poly I:C group than those in the saline and heat-exposed groups on day 7, although the amount of interleukin-1β mRNA showed no differences. Serum adrenocorticotropic hormone and catecholamine levels were not significantly different between groups. The present results indicate that the prolonged fatigue induced by poly I:C, which is evaluated by the spontaneous running wheel activity, can be used as an animal model for the immunologically induced fatigue associated with viral infection, and suggest that brain IFN-α may play a role in this model.