title: Differential respiratory control of the upper airway and diaphragm muscles induced by 5-HT1A receptor ligands.
abstract: BACKGROUND
  Serotonin (5-HT) has a role in respiratory function and dysfunction. Although 5-HT affects respiratory drive to both phrenic and cranial motoneurons, relatively little is known about the role of 5-HT receptor subtypes in the control of upper airway muscle (UAM) respiratory activity.
  
  
  METHODS
  Here, we performed central injections of 5-HT1A agonist (8-OHDPAT) or antagonist (WAY100635) in anesthetized rats and analyzed changes in the electromyographic activity of several UAM and other cardiorespiratory parameters. We also compared the pattern of Fos expression induced after central injection of a control solution or 8-OHDPAT.
  
  
  RESULTS
  Results showed that 8-OHDPAT induced a robust increase in UAM activity, associated with either tachypnea under volatile anesthesia or bradypnea under liquid anesthesia. Injection of WAY100635 switched off UAM respiratory activity and led to bradypnea, suggesting a tonic excitatory role of endogenous 5-HT1A receptor activation. Co-injection of the agonist and the antagonist blocked the effects produced by each drug alone. Besides drug-induced changes in respiratory frequency, only slight increases in surface of diaphragm bursts were observed. Significant increases in Fos expression after 5-HT1A receptor activation were seen in the nucleus tractus solitarius, nucleus raphe pallidus, parapyramidal region, retrotrapezoid nucleus, lateral parabrachial, and Kölliker-Fuse nuclei. This restricted pattern of Fos expression likely identified the neural substrate responsible for the enhancement of UAM respiratory activity observed after 8-OHDPAT injection.
  
  
  CONCLUSIONS
  These findings suggest an important role for the 5-HT1A receptors in the neural control of upper airway patency and may be relevant to counteract pharyngeal atonia during obstructive sleep apneas.
authors.affiliation: INSERM, ERI27, Université de Caen, CHRU Caen, Explorations Fonctionnelles, Caen, France. stephane.besnard@unicaen.fr
authors.forename: Stephane
authors.initials: S
authors.lastname: Besnard
authors.forename: Hanan
authors.initials: H
authors.lastname: Khemiri
authors.forename: Fabienne
authors.initials: F
authors.lastname: Masse
authors.forename: Pierre
authors.initials: P
authors.lastname: Denise
authors.forename: Marion
authors.initials: M
authors.lastname: Verdaguer
authors.forename: Christian
authors.initials: C
authors.lastname: Gestreau
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology*; D004576:Electromyography / Q000187:drug effects*; D007267:Injections; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin