Am. J. Respir. Crit. Care Med.,
Volume 157, Number 3, March 1998, 917-920
Diazepam Suppresses Sleep Apneas in Rats
DAVID W.
CARLEY,
SINISA M.
TRBOVIC,
and
MIODRAG
RADULOVACKI
Department of Medicine, Section of Respiratory and Critical Care Medicine, and Department of Pharmacology, University of
Illinois College of Medicine at Chicago, Chicago, Illinois
To test the respiratory effects of benzodiazepines in an established animal 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 stimulation, non-REM-related spontaneous and post-sigh apnea expression decreased following each dose of diazepam (p = 0.006 to 0.04), but REM-related 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 increased (p = 0.03) and REM sleep was decreased (p = 0.009). We conclude that both hypnotic and non-hypnotic
doses of benzodiazepines may be associated with suppression of sleep-related central apnea. We further conclude that non-REM and REM-related apneas arise from at least partially distinct mechanisms.
