Serotonergic stimulation of the genioglossus and the response to nasal continuous positive airway pressure

In obstructive sleep apnea (OSA), abnormal pharyngeal collapsibility may be offset by increased mechanoreflex-mediated activity of dilator muscles whi le awake, but this reflex is inhibited during sleep and during application of nasal continuous positive airway pressure (CPAP). Direct activation of u pper airway (UA) motor neurons in the hypoglossal nucleus by a selective se rotonin reuptake inhibitor (SSRI), paroxetine hydrochloride, may increase g enioglossal electromyographic (EMC) activity (EMGgg) in a manner resistant to mechanoreflex inhibition. We studied the effects of paroxetine on EMGgg using an intraoral surface electrode during eupnea or room air breathing (R A), hypercapnia (HYP), and CPAP application in the presence of hypercapnia (CPAP + HYP) in 11 normal volunteers, using a double-blind, placebo-control led crossover design. After 5 d of paroxetine, EMGgg activity increased sig nificantly within each condition (p = 0.02). EMGgg during the conditions of HYP and HYP + CPAP were significantly greater than during RA for both plac ebo and paroxetine treatments (p = 0.006). EMGgg activity in HYP persisted during HYP + CPAP on paroxetine (183% versus 182% of placebo, respectively) . We conclude that paroxetine produces an augmentation in EMGgg in normal s ubjects during wakefulness and that this effect persists during mechanorefl ex inhibition. This is consistent with a central serotonergic effect.