DIAZEPAM SUPPRESSES SLEEP APNEAS IN RATS

To test the respiratory effects of benzodiazepines in an established a nimal model of central apnea, we administered nonhypnotic and hypnotic doses of diazepam to nine adult male Sprague-Dawley rats chronically instrumented for sleep staging. In random order on separate days, rats were recorded following intraperitoneal injection of: (1) saline; (2) 0.05 mg/kg diazepam; or (3) 5 mg/kg diazepam. Normalized inspiratory minute ventilation increased significantly during wakefulness and non- rapid eye movement (non-REM) sleep following each dose of diazepam (p < 0.003 in each case) and following the highest dose during rapid eye movement (REM) sleep (p = 0.01). In accord with this respiratory stimu lation, non-REM-related spontaneous and post-sigh apnea expression dec reased following each dose of diazepam (p = 0.006 to 0.04), but REM-re lated apnea expression was unaffected despite significant respiratory stimulation. The durations of non-REM and REM sleep were unaffected by the low dose, but following 5 mg/kg of diazepam non-REM sleep was inc reased (p = 0.03) and REM sleep was decreased (p = 0.009). We conclude that both hypnotic and non-hypnotic doses of benzodiazepines may be a ssociated with suppression of sleep-related central apnea. We further conclude that non-REM and REM-related apneas arise from at least parti ally distinct mechanisms.