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

doi:10.1016/S0306-4522(03)00365-8

Neuroscience

Volume 120, Issue 3, 1 September 2003, Pages 837-845

https://doi.org/10.1016/S0306-4522(03)00365-8 Get rights and content

Abstract

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.

Section snippets

Animals

Male Wistar rats weighing 250–300 g were housed individually in plastic cages (25×42×18 cm) at a temperature of 23–25 °C with 12-h light/dark cycle (light on at 08:00 h) and had free access to a laboratory chow and water. Each cage contains 30-cm-diameter running wheel (SW-30; Melquest Inc., Toyama, Japan) and rats can enter the wheel any time. The number of wheel turns per minute was counted using analog/digital interface (CIF-32) and computer software from Melquest Inc. Experiments started

Effects of poly I:C on running wheel activity

As shown in Fig. 1, an actogram of a rat given i.p. injection of poly I:C (3 mg/kg) demonstrated a decrease in running wheel activity after the injection performed on day 1, lasting for at least 1 week. To further analyze the pattern of running activity, histograms for the number of wheel turns in 1-min bin (w.t./min) were made from data on days (−2), 1, and 7. As shown in Fig. 2A, upper, there were two peaks of 6 and one w.t./min before poly I:C on day (−2). The raw data indicated that the

Discussion

Voluntary running in the wheel is a highly motivated activity in rats, which run about 800–1800 w.t./day in normal condition. The present results indicated that i.p. injection of poly I:C (3 mg/kg) in rats induced a decrease in daily amount of spontaneous running wheel activity to about 40–60% of the preinjection level until day 9, while circadian rhythm of the activity was maintained. The running wheel activity gradually returned to the baseline level by day 14. mRNA for IFN-α increased in the

Acknowledgements

This work was supported by Grant-in Aid for Scientific Research (14657018 and 12470011 (B) to T.K.) and Special Coordination Funds of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.

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

Abstract

Section snippets

Animals

Effects of poly I:C on running wheel activity

Discussion

Acknowledgements

J Neuroimmunol

Brain Res

Clin Immunol Immunopathol

J Biol Chem

Brain Res

Am J Med

Am J Med

Neurochem Int

Am J Med

Brain Res

Eur J Pharmacol

Physiol Behav

Trends Neurosci

Clin Immunol Immunopathol

Am J Med

Neurosci Lett

Brain Res Bull

Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3

Nature

Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytrptamine metabolism in six different brain regions in the rat

Acta Physiol Scand

Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells

J Neurochem