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.
|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|
|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|
|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|
Showing the most recent 10 out of 39 publications