Role of endogenous serotonin in modulating genioglossus muscle activity in awake and sleeping rats.
BACKGROUND
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.


OBJECTIVE
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 (100 microM).


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. We also demonstrated a significant serotonergic drive modulating GG activity in vagotomized rats, but not in vagi-intact rats, under anesthesia, 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 pharmacologic strategies aiming to increase GG activity by manipulating endogenous serotonin in patients with obstructive sleep apnea.
Sood
Sandeep
S
Department of Medicine, University of Toronto, Toronto, Canada.
Morrison
Janna L
JL
Liu
Hattie
H
Horner
Richard L
RL
D000818:Animals; D007002:Hypoglossal Nerve / Q000502:physiology*; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012895:Sleep, REM / Q000502:physiology; D014748:Vinca Alkaloids; D014851:Wakefulness / Q000502:physiology
D012702:Serotonin Antagonists; C107224:VA 033; D014748:Vinca Alkaloids; D008803:Mianserin; D012701:Serotonin