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Am J Physiol Regul Integr Comp Physiol 280: R1213-R1220, 2001;
0363-6119/01 $5.00
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Vol. 280, Issue 4, R1213-R1220, April 2001

Vagotomy attenuates tumor necrosis factor-alpha -induced sleep and EEG delta -activity in rats

Takeshi Kubota, Jidong Fang, Zhiwei Guan, Richard A. Brown, and James M. Krueger

Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington 99164-6520

Much evidence suggests that tumor necrosis factor-alpha (TNF-alpha ) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-alpha induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-alpha had not heretofore been studied. Four doses of TNF-alpha were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-alpha (50, 100, and 200 µg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-alpha increased EEG delta -power and decreased EEG alpha - and beta -power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 µg/kg of TNF-alpha were attenuated, while significant TNF-alpha -induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG delta -power induced by TNF-alpha intraperitoneally. These results suggest that peripheral TNF-alpha can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-alpha and EEG synchronization on sleep. Intraperitoneal TNF-alpha failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-alpha -induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.

electroencephalogram; brain; vagus nerve


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