title: State-dependent vs. central motor effects of ethanol on breathing.
abstract: Ethanol, one of the most widely used drugs in Western society, worsens obstructive sleep apnea in humans. No studies, however, have distinguished between two primary mechanisms that could mediate suppression of genioglossus (GG) activity with ethanol. We test the hypothesis that ethanol suppresses GG activity by effects at the hypoglossal motor pool and/or by state-dependent regulation of motor activity via independent influences on sleep/arousal processes. Intraperitoneal injections of ethanol (1.25 g/kg, n = 6 rats) resulted in maximum blood levels of 125.5 +/- 15.8 mg/dl, i.e., physiologically relevant levels for producing behavioral impairment in rats and humans. Ethanol decreased wakefulness, reduced sleep latency, and increased non-rapid eye movement sleep (P < 0.001, n = 10 rats) and significantly reduced postural muscle tone and electroencephalogram frequencies, consistent with sedation. Ethanol also caused a state-dependent (wakefulness only) decrease in respiratory-related GG activity (P = 0.018) but did not affect diaphragm amplitude or rate, with the magnitude of GG decrease related to baseline activity (P < 0.0002). Ethanol did not alter GG activity when applied to the hypoglossal motor pool (0.025-1 M, n = 16 isoflurane-anesthetized rats). In conclusion, ethanol promoted sleep and altered electroencephalogram and postural motor activities, indicative of sedation. The lack of effect on GG with ethanol at the hypoglossal motor pool indicates that the GG and postural motor suppression following systemic administration was mediated via effects on state-dependent/arousal-related processes. These data show that ethanol can suppress GG by primary influences on state-dependent aspects of central nervous system function independent of effects on the respiratory network per se, a distinction that has not previously been identified experimentally.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Vecchio
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Grace
authors.forename: Hattie
authors.initials: H
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
authors.forename: Anh D
authors.initials: AD
authors.lastname: Lê
authors.forename: Richard L
authors.initials: RL
authors.lastname: Horner
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D000431:Ethanol