8-OH-DPAT suppresses spontaneous central apneas in the C57BL/6J mouse strain

Respir Physiol Neurobiol. 2008 Mar 20;161(1):10-5. doi: 10.1016/j.resp.2007.11.001. Epub 2007 Nov 17.

Abstract

Apneas are common and prognostically relevant disorders of the central control of breathing, but pharmacological interventions are dissatisfying. The respiratory phenotype of C57BL/6J mice is characterized by the occurrence of spontaneous central apneas with laryngeal closure. In the present study we investigated the impact of the 5-HT(1A) receptor agonist 8-OH-DPAT on apneas in C57BL/6J mice, because of the important role of serotonin in the regulation of breathing and previous reports showing that serotonergic drugs can affect central apneas. Whole-body plethysmography in awake, unrestrained mice revealed that intraperitoneal application of 8-OH-DPAT (10microgkg(-1)) decreased the occurrence of spontaneous apneas from 1.91+/-0.25 to 1.05+/-0.05 apneas min(-1). The efficacy of 5-HT(1A) receptor activation was further verified in the in situ working heart-brainstem preparation. Here the apneas occurred at a frequency of 1.33+/-0.19min(-1). Intra-arterial perfusion with 1-2microM 8-OH-DPAT completely abolished spontaneous apneas. These results suggest that 5-HT(1A) receptor activation may be a potential treatment option for central apneas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Mice
  • Mice, Inbred C57BL
  • Plethysmography, Whole Body
  • Serotonin Receptor Agonists / pharmacology*
  • Sleep Apnea, Central / drug therapy*

Substances

  • Serotonin Receptor Agonists
  • 8-Hydroxy-2-(di-n-propylamino)tetralin