Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-alpha mRNA in rats: a model for immunologically induced fatigue.
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 degrees 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-alpha (IFN-alpha) 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-1 beta 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-alpha may play a role in this model.
Katafuchi
T
T
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. kataf@physiol.med.kyushu-u.ac.jp
Kondo
T
T
Yasaka
T
T
Kubo
K
K
Take
S
S
Yoshimura
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature; D001835:Body Weight; D001921:Brain / Q000276:immunology*; D002395:Catecholamines / Q000097:blood; D002908:Chronic Disease; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005221:Fatigue / Q000276:immunology*; D007031:Hypothalamus / Q000276:immunology; D016898:Interferon-alpha / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D009043:Motor Activity; D011070:Poly I-C; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012420:Running
D002395:Catecholamines; D016898:Interferon-alpha; D007375:Interleukin-1; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D011070:Poly I-C