title: Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs.
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.
authors.affiliation: Department of Psychiatry and Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: John
authors.forename: M F
authors.initials: MF
authors.lastname: Wu
authors.forename: J M
authors.initials: JM
authors.lastname: Siegel
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000008:administration & dosage*; D002385:Cataplexy / Q000188:drug therapy* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D004585:Electrooculography / Q000187:drug effects; D005260:Female; D007275:Injections, Intravenous; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009290:Narcolepsy / Q000188:drug therapy* / Q000503:physiopathology; D009479:Neuropeptides / Q000008:administration & dosage*; D000068797:Orexins; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins