Vagotomy attenuates tumor necrosis factor-a-induced sleep and EEG d-activity in rats

Kubota, Takeshi, Jidong Fang, Zhiwei Guan, Richard A. Brown, and James M. Krueger. Vagotomy attenuates tumor necrosis factor-a-induced sleep and EEG d-activity in rats. Am J Physiol Regulatory Integrative Comp Physiol 280: R1213–R1220, 2001.—Much evidence suggests that tumor necrosis factor-a (TNF-a) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-a induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-a had not heretofore been studied. Four doses of TNF-a were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-a (50, 100, and 200 mg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-a increased EEG d-power and decreased EEG aand b-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 mg/kg of TNF-a were attenuated, while significant TNF-a-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG d-power induced by TNF-a intraperitoneally. These results suggest that peripheral TNF-a can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-a and EEG synchronization on sleep. Intraperitoneal TNF-a failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-a-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.