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Published ahead of print on July 14, 2005, doi:10.1164/rccm.200502-258OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 10, November 2005, 1338-1347

A more recent version of this article appeared on November 15, 2005
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Submitted on February 16, 2005
Accepted on July 14, 2005

Role of Endogenous Serotonin in Modulating Genioglossus Muscle Activity in Awake and Sleeping Rats

Sandeep Sood1, Janna L Morrison1, Hattie Liu1, and Richard L Horner1*

1 Departments of Medicine and Physiology, University of Toronto, Toronto, ON, Canada

* To whom correspondence should be addressed. E-mail: richard.horner{at}utoronto.ca.

Rationale: Exogenous serotonin at the hypoglossal motor nucleus (HMN) stimulates genioglossus (GG) muscle activity. However, whether endogenous serotonin contributes to GG activation across natural sleep-wake states has not been determined, but is relevant given that serotonergic neurons have decreased activity in sleep and project to pharyngeal motoneurons. Objectives: To determine the role of endogenous serotonin at the HMN in modulating GG activity across natural sleep-wake states. Methods: Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the HMN for perfusion of artificial-cerebrospinal-fluid and the serotonin receptor antagonist mianserin (100µM). Measurements and Main Results: In room air there was no effect of mianserin on respiratory-related or tonic GG activities across sleep-wake states (P>0.300). In hypercapnia, however, the normal declines in GG activity from non-REM to REM sleep, and wakefulness to REM sleep were reduced with mianserin (P<0.005). These data demonstrate a normally low endogenous serotonergic drive modulating GG activity unless augmented by reflex inputs. Under anesthesia we also demonstrated a significant serotonergic drive modulating GG activity in vagotomised rats but not in vagi intact rats, suggesting that previous results in reduced preparations may have been influenced by vagotomy. Conclusions: The results show a minimal endogenous serotonergic drive at the HMN modulating GG activity across sleep-wake states, unless augmented by reflex inputs. This result has implications for pharmacological strategies aiming to increase GG activity by manipulating endogenous serotonin in obstructive sleep apnea patients.
Key words: Sleep, Hypoglossal Motor Nucleus, Serotonin, Obstructive Sleep Apnea




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