Objective: To determine whether certain sedatives may, by increasing arousal threshold, allow pharyngeal dilator muscle activity to increase more in response to chemical stimuli before arousal occurs. Design, Participants and Interventions: Thirteen chronically instrumented rats were studied during sleep following injections of placebo or sedating doses of pentobarbital (10mg/kg). Intermittently, inspired CO 2 was increased gradually until arousal occurred. Measurements and Results: Maximum

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... oglossus activity reached before arousal was higher with pentobarbital than placebo (34.5 ± 24.3 vs 3.7 ± 2.9mV; P<0.001) for 2 reasons. First, genioglossus activity was greater during undisturbed sleep before CO 2 was applied (23.3 ± 15.3 vs 2.5 ± 1.5 mV, P<0.001). When sleep periods were long, a ramp-like increase in genioglossus activity (GG-Ramp) began and progressed until arousal. GG-Ramps developed with both placebo and pentobarbital but reached higher levels with pentobarbital due to longer sleep periods and faster increase in genioglossus activity during the ramp. GG-Ramps began when diaphragm activity was lowest and progressed despite unchanged diaphragm activity. Second, as hypothesized, the increase in genioglossus activity with CO 2 before arousal was greater than with placebo (11.2 ± 2.5 vs 1.2 ± 2.5mV; P<0.05) due to increased arousal threshold. In 27 of 126 CO 2 challenges delivered while GG-Ramps were in progress, genioglossus activity paradoxically decreased despite increased diaphragmatic activity. These negative responses occurred randomly in 7 of 13 rats. Conclusions: In rats: 1) Sedatives may allow genioglossus activity to reach higher levels during sleep. 2) A time-dependent increase in genioglossus activity occurs during undisturbed sleep that is unrelated to chemical drive. 3) Transient hypercapnia may elicit inhibition of genioglossus activity under currently unidentified circumstances.