title: Diazepam suppresses sleep apneas in rats.
abstract: 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.
authors.affiliation: Department of Medicine, University of Illinois College of Medicine at Chicago, 60612, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Carley
authors.forename: S M
authors.initials: SM
authors.lastname: Trbovic
authors.forename: M
authors.initials: M
authors.lastname: Radulovacki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003975:Diazepam / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000627:therapeutic use*; D001239:Inhalation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012891:Sleep Apnea Syndromes / Q000503:physiopathology / Q000517:prevention & control*; D012894:Sleep Stages / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D012965:Sodium Chloride; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D012965:Sodium Chloride; D003975:Diazepam