Abstract

The Stanford University Sleep Disorders Center has established a colony of dogs affected with a genetically transmitted form of narcolepsy. We now propose extensive in vivo and in vitro pharmacological investigations utilizing this animal model in order to further understand the neurotransmitter defects in narcolepsy and to elaborate new therapeutic strategies for human narcolepsy.
The specific aims of this project are: * To study the effects of monoaminergic and muscarinic agonists and antagonists selective for receptor subtypes on canine cataplexy. * To study the binding properties of these agents in vitro and to correlate these properties with in vivo effects on canine cataplexy. * To study the influence of nighttime sleep on daytime canine cataplexy. Nighttime sleep will be manipulated by various alerting and hypnogenic drugs (especially those increasing REM sleep). A key variable will be the intensity of cataplexy on the following day. * To study the effect of prazosin (an alpha 1 antagonist) and yohimbine (an alpha 2 antagonist) on human narcoleptic patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027710-03
Application #
3414110
Study Section
Neurology C Study Section (NEUC)
Project Start
1989-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Vankova, Jitka; Stepanova, Iva; Jech, Robert et al. (2003) Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C. Sleep 26:427-30
Nishino, Seiji; Ripley, Beth; Mignot, Emmanuel et al. (2002) CSF hypocretin-1 levels in schizophrenics and controls: relationship to sleep architecture. Psychiatry Res 110:1-7
Fujiki, N; Yoshida, Y; Ripley, B et al. (2001) Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 hours and in response to food deprivation. Neuroreport 12:993-7
Okura, M; Fujiki, N; Ripley, B et al. (2001) Narcoleptic canines display periodic leg movements during sleep. Psychiatry Clin Neurosci 55:243-4
Nishino, S; Ripley, B; Overeem, S et al. (2001) Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy. Ann Neurol 50:381-8
Nishino, S; Fujiki, N; Ripley, B et al. (2001) Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs. Neurosci Lett 313:125-8
Ripley, B; Overeem, S; Fujiki, N et al. (2001) CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology 57:2253-8
Ripley, B; Fujiki, N; Okura, M et al. (2001) Hypocretin levels in sporadic and familial cases of canine narcolepsy. Neurobiol Dis 8:525-34
Yoshida, Y; Fujiki, N; Nakajima, T et al. (2001) Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur J Neurosci 14:1075-81
Melberg, A; Ripley, B; Lin, L et al. (2001) Hypocretin deficiency in familial symptomatic narcolepsy. Ann Neurol 49:136-7

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