Vagotomy attenuates tumor necrosis factor-α-induced sleep and EEG δ-activity in rats

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

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)R1213-R1220
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4 49-4
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)


Dive into the research topics of 'Vagotomy attenuates tumor necrosis factor-α-induced sleep and EEG δ-activity in rats'. Together they form a unique fingerprint.

Cite this