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Time- and dose-related effects of three 5-HT receptor ligands on the genioglossus activity in anesthetized and conscious rats

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Abstract

Clinical trials in obstructive sleep apnea syndrome patients reported moderate effects of serotoninergic drugs on oropharyngeal apneas, although numerous specific 5-HT ligands highly modulate the genioglossus muscle (GG) activity in experiments performed in anesthetized animals. The purpose of this study was to investigate time- and dose-related effects of central and systemic injections of 8-OHDPAT (5-HT1A agonist), SB224289 (5-HT1B antagonist), and DOI (5-HT2A/2C agonist) on the GG activity in anesthetized and conscious rats. Electromyographic recordings of the GG activity (GGemg) were analyzed after central and systemic injections of each drug in ketamine–xylazine anesthetized rats. Electroencephalograms (EEG), as well as neck and GG muscle activities (Nemg and GGemg), were recorded in 15 additional rats to analyze changes in sleep–wake states before and after systemic injection of the drugs. Central injections of 8-OHDPAT and DOI in anesthetized rats induced clear dose-related increases in phasic and tonic GGemg activities, respectively. The time-responses were inferior to 30 min with 8-OHDPAT and over 50 min with DOI. Moderate increases in phasic GGemg activity were also observed after central, but not peripheral injection of SB and DOI. The total sleep time measured in conscious rats significantly decreased after systemic injections of DOI and 8-OHDPAT, although no change was observed in phasic or tonic GGemg activity. The dose- and time-responses of the DOI in anesthetized rat partly explain the lack of GGemg tonic change in conscious rat. The moderate effect on the GGemg phasic activity of peripheral 5-HT1A ligand injection easily explains the lack of change in conscious rat. The serotonergic modulation of the respiratory component of the GGemg remains complex, but is highly sensitive to 5-HT1A receptors after central injection in rats under anesthesia. Forthcoming therapy in OSAS should be made of mixed profiled neurotransmitters and different routes of administration.

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Acknowledgments

The authors thank Dr. Adèle Ottavi and Me Mathilde Beslier for their help in the manuscript preparation. This study was supported by a grant from Sanofi-Aventis (sleep research award “Veille-Sommeil” French Sleep Research Society Congress SFRS, Paris, France 2003).

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Authors and Affiliations

  1. Neurophysiologie Clinique-Sommeil CHU de Poitiers, Université de Poitiers, 2 rue de la Milétrie, 86021, Poitiers cedex, France

    S. Besnard, M. Verdaguer, B. Cappelin & J. C. Meurice

  2. Laboratoire de neurobiologie de l’anxiété et de la dépression, Faculté de Médecine, Université de Nantes, 1, rue Gaston Veil, 44035, Nantes Cedex 1, France

    F. Massé

  3. Laboratoire de Physiologie Neurovegetative, UMR CNRS 6153 INRA 1147, Universite Paul Cezanne Aix-Marseille III, Av. Escadrille Normandie-Niemen, 13397, Marseille Cedex 20, France

    C. Gestreau

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  1. S. Besnard
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Correspondence to S. Besnard.

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Besnard, S., Massé, F., Verdaguer, M. et al. Time- and dose-related effects of three 5-HT receptor ligands on the genioglossus activity in anesthetized and conscious rats. Sleep Breath 11, 275–284 (2007). https://doi.org/10.1007/s11325-007-0107-0

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