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Genioglossus muscle activity and serotonergic modulation of hypoglossal motor output in obese Zucker rats

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

Submitted 30 October 2006 ; accepted in final form 26 February 2007

Obese Zucker rats have a narrower and more collapsible upper airway compared with lean controls, similar to obstructive sleep apnea (OSA) patients. Genioglossus (GG) muscle activity is augmented in awake OSA patients to compensate for airway narrowing, but the neural control of GG activity in obese Zucker rats has not been investigated to determine whether such neuromuscular compensation also occurs. This study tests the hypotheses that GG activity is augmented in obese Zucker rats compared with lean controls and that endogenous 5-hydroxytryptamine (5-HT) contributes to GG activation. Seven obese and seven lean Zucker rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and they were implanted with GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid and the 5-HT receptor antagonist mianserin (100 µM). Compared with lean controls, respiratory rates were increased in obese rats across sleep-wake states (P = 0.048) because of reduced expiratory durations (P = 0.007); diaphragm activation was similar between lean and obese animals (P = 0.632). Respiratory-related, tonic, and peak GG activities were also similar between obese and lean rats (P > 0.139). There was no reduction in GG activity with mianserin at the hypoglossal motor nucleus, consistent with recent observations of a minimal contribution of endogenous 5-HT to GG activity. These results suggest that despite the upper airway narrowing in obese Zucker rats, these animals have a sufficiently stable airway such that pharyngeal muscle activity is normal across sleep-wake states.

sleep; hypoglossal motor nucleus; genioglossus muscle; serotonin; obesity; obstructive sleep apnea

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