Low-dose mirtazapine increases genioglossus activity in the anesthetized rat

Study Objectives: To examine the effects of mirtazapine on genioglossus and diaphragmatic electromyogram activity in the anesthetized rat. Design: Parallel-group study. Subjects: Sprague-Dawley adult male rats, 10 in each of 3 groups were studied. Interventions: After anesthesia with 1.2 g/kg of urethane, a tracheostomy and bilateral vagotomy were performed. Femoral arterial and venous lines were placed, and fine wire hook electrodes were implanted into the genioglossus and diaphragm muscles. Measurements: After a baseline period of measurement, either saline, 0.5 mg/kg of mirtazapine, or 5.0 mg/kg of mirtazapine was injected via the intraperitoneal route, and measurements were made for the next 3 hours. The average peak and tonic values of the moving time average of the genioglossus and diaphragm electromyogram for hours 1, 2, and 3 were determined and expressed as a percentage of the corresponding average value during the baseline (preinjection) monitoring period. Results: At 0.5 mg/kg of mirtazapine, the peak genioglossus electromyogram was significantly higher than in control conditions over hours 2 and 3. At 5.0 mg/kg of mirtazapine, the genioglossus electromyogram was significantly lower than in control conditions for the first 2 hours of monitoring. The peak diaphragmatic electromyogram was slightly but significantly lower in the mirtazapine 5.0-mg/kg group than in controls. Conclusions: Mirtazapine, at a dose similar to one used clinically, increased genioglossus activity. We hypothesize that, at this dose, the ability of mirtazapine to increase serotonin and norepinephrine or block type-3 serotonin receptors predominated. At the higher dose of mirtazapine, the type-2 blockade effect predominated and genioglossus activity decreased.