title: Is narcolepsy a REM sleep disorder? Analysis of sleep abnormalities in narcoleptic Dobermans.
abstract: Narcolepsy is a chronic sleep disorder marked by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Since the discovery of sleep onset REM periods (SOREMPs) in narcoleptic patients, narcolepsy has often been regarded as a disorder of REM sleep generation: REM sleep intrudes in active wake or at sleep onset, resulting in cataplexy, sleep paralysis, or hypnagogic hallucinations. However, this hypothesis has not been experimentally verified. In the current study, we characterized the sleep abnormalities of genetically narcoleptic-cataplectic Dobermans, a naturally occurring animal model of narcolepsy, in order to verify this concept. Multiple sleep latency tests during the daytime revealed that narcoleptic Dobermans exhibit a shorter sleep latency and a higher frequency of SOREMPs, compared to control Dobermans. The total amount of time spent in wake and sleep during the daytime is not altered in narcoleptic dogs, but their wake and sleep patterns are fragmented, and state transitions into and from wake and other sleep stages are altered. A clear 30 min REM sleep cyclicity exists in both narcoleptic and control dogs, suggesting that generation of the ultradian rhythm of REM sleep is not altered in narcoleptics. In contrast, cataplexy displays no cyclicity and can be elicited in narcoleptic animals anytime with emotional stimulation and displays no cyclicity. Stimulation of a cholinoceptive site in the basal forebrain induces a long-lasting attack of cataplexy in narcoleptic dogs; however, bursts of rapid eye movements during this state still occur with a 30 min cyclicity. Sites and mechanisms for triggering cataplexy may therefore be different from those for REM sleep. Cataplexy and a dysfunction in the maintenance of vigilance states, but not abnormal REM sleep generation, may therefore be central to narcolepsy.
authors.affiliation: Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, 1201 Welch Road, MSLS Building Room P113, Palo Alto, CA 94304-5485, USA. nishino@leland.stanford.edu
authors.forename: S
authors.initials: S
authors.lastname: Nishino
authors.forename: J
authors.initials: J
authors.lastname: Riehl
authors.forename: J
authors.initials: J
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Kwan
authors.forename: M
authors.initials: M
authors.lastname: Reid
authors.forename: E
authors.initials: E
authors.lastname: Mignot
mesh_terms: D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D002217:Carbachol / Q000494:pharmacology; D002385:Cataplexy / Q000139:chemically induced / Q000503:physiopathology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D004285:Dogs / Q000502:physiology*; D009290:Narcolepsy / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology*
chemical_list: D018679:Cholinergic Agonists; D002217:Carbachol