Abstract
Recent work has implicated the hypocretin (orexin) system in the genesis of narcolepsy. In the current study we demonstrate that systemically administered hypocretin-1 (Hcrt-1) produces an increase in activity level, longer waking periods, a decrease in REM sleep without change in nonREM sleep, reduced sleep fragmentation and a dose dependent reduction in cataplexy in canine narcoleptics. Repeated administration of single daily doses of Hcrt-1 led to consolidation of waking and sleep periods and to a complete loss of cataplexy for periods of three or more days after treatment in animals that were never asymptomatic under control conditions. Systemic administration of Hcrt-1 may be an effective treatment for narcolepsy.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Carrier Proteins / administration & dosage*
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Cataplexy / drug therapy*
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Cataplexy / physiopathology
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Circadian Rhythm / drug effects
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Disease Models, Animal
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Dogs
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Dose-Response Relationship, Drug
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Electroencephalography / drug effects
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Electromyography / drug effects
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Electrooculography / drug effects
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Female
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Injections, Intravenous
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Intracellular Signaling Peptides and Proteins*
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Male
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Motor Activity / drug effects
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Narcolepsy / drug therapy*
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Narcolepsy / physiopathology
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Neuropeptides / administration & dosage*
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Orexins
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Sleep / drug effects*
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Sleep Stages / drug effects
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Treatment Outcome
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Wakefulness / drug effects*
Substances
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Neuropeptides
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Orexins