Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs.
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.
John
J
J
Department of Psychiatry and Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
Wu
M F
MF
Siegel
J M
JM
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*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins