title: 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-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.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, University Medicine Göttingen, Georg August University, Robert-Koch-Str. 40, 37075 Göttingen, Germany. georg.stettner@med.uni-goettingen.de
authors.forename: Georg M
authors.initials: GM
authors.lastname: Stettner
authors.forename: Sébastien
authors.initials: S
authors.lastname: Zanella
authors.forename: Gérard
authors.initials: G
authors.lastname: Hilaire
authors.forename: Mathias
authors.initials: M
authors.lastname: Dutschmann
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D010993:Plethysmography, Whole Body; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D020182:Sleep Apnea, Central / Q000188:drug therapy*
chemical_list: D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin