The orexin receptor 1 (OX1R) in the rostral medullary raphe contributes to the hypercapnic chemoreflex in wakefulness, during the active period of the diurnal cycle

Respir Physiol Neurobiol. 2010 Jan 31;170(1):96-102. doi: 10.1016/j.resp.2009.12.002. Epub 2009 Dec 6.

Abstract

It has been shown that orexin plays an important role in the hypercapnic chemoreflex during wakefulness, and OX(1)Rs in the retrotrapezoid nucleus (RTN) participate in this mechanism. We hypothesized that OX(1)R in the rostral medullary raphe (MR) also contributes to the hypercapnic chemoreflex. We studied the effects on ventilation in air and in 7% CO(2) of focal antagonism of OX(1)R in the rostral MR by microdialysis of SB-334867 in rats during wakefulness and NREM sleep, under dark and light periods. During wakefulness in the dark period, but not in the light period, SB-334867 caused a 16% reduction of the hyperventilation induced by 7% CO(2) compared with vehicle. There was no significant effect in sleep. The basal ventilation, body temperature and V(O2) were not affected. No effect was observed in a separate group of animals which had the microdialysis probe misplaced (peri-raphe). We conclude that OX(1)R in the rostral medullary raphe contribute to the hypercapnic chemoreflex in wakefulness, during the dark period in rats.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzoxazoles / pharmacology
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / physiology
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Electroencephalography / methods
  • Electromyography / methods
  • Hypercapnia / pathology*
  • Hypercapnia / physiopathology
  • Male
  • Microdialysis / methods
  • Naphthyridines
  • Orexin Receptors
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / physiology
  • Pulmonary Ventilation / drug effects
  • Pulmonary Ventilation / physiology*
  • Raphe Nuclei / cytology
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / metabolism*
  • Sleep Stages / drug effects
  • Urea / analogs & derivatives
  • Urea / pharmacology
  • Wakefulness / physiology*

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Hcrtr1 protein, rat
  • Naphthyridines
  • Orexin Receptors
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea