Low-dose mirtazapine increases genioglossus activity in the anesthetized rat.
OBJECTIVE
To examine the effects of mirtazapine on genioglossus and diaphragmatic electromyogram activity in the anesthetized rat.


METHODS
Parallel-group study.


METHODS
Sprague-Dawley adult male rats, 10 in each of 3 groups were studied.


METHODS
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.


METHODS
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.
Berry
Richard B
RB
Malcom Randall VAMC/University of Florida College of Medicine, Gainesville 32610, USA. sleep_doc@msn.com
Koch
Gary L
GL
Hayward
Linda F
LF
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000818:Animals; D003964:Diaphragm / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078785:Mirtazapine; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014059:Tongue / Q000187:drug effects* / Q000294:innervation*; D014139:Tracheostomy; D014520:Urethane / Q000008:administration & dosage; D014628:Vagotomy
D000317:Adrenergic alpha-Antagonists; D018686:Anesthetics, Intravenous; D008803:Mianserin; D014520:Urethane; D000078785:Mirtazapine