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

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-HT1A 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 (10 mu g kg(-1)) decreased the occurrence of spontaneous apneas from 1.91 +/- 0.25 to 1.05 +/- 0.05 apneas min(-1). The efficacy of 5-HT1A receptor activation was further verified in the in situ working heart-brainstem preparation. Here the apneas occurred at a frequency of 1.33 +/- 0.19 min(-1). Intra-arterial perfusion with 1-2 mu M 8-OH-DPAT completely abolished spontaneous apneas. These results suggest that 5-HT1A receptor activation may be a potential treatment option for central apneas. (C) 2007 Elsevier B.V. All rights reserved.