This proposal seeks continuation of support for maintenance of an indispensable national resource--a colony of dogs which provides the only existing animal model of the human disease of narcolepsy. These animals manifest the identical pathognomonic signs found in human narcolepsy (namely, sleep onset REM periods and bouts of cataplexy) and genetically transmit this trait. Recent research investigations have identified specific neurochemical defects in the brains of affected animals that may reflect the underlying neural basis of this disease. We plan to maintain a breeding colony of 25 dogs with heritable narcolepsy for five years and a research colony of 80 narcoleptic dogs/year reared to 100 days of age. The dog breeds that will be maintained are Doberman pinschers, Labrador retrievers, and Labrador-Doberman mixtures, all of which transmit the narcoleptic trait genetically. The narcoleptic dog colony is a necessary resource for current and future projects for both Stanford and extra-Stanford investigators. It is the only colony of narcoleptic animals in the world. The research projects made possible by the existence of this colony will elucidate the neurochemical and genetic causes of narcolepsy, clarify the mechanisms of symptoms, such as excessive sleepiness and hallucinations, present in other human illnesses, and provide insights into the basic mechanisms of sleep.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015184-08
Application #
3396031
Study Section
(SSS)
Project Start
1980-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Nishino, S; Shelton, J; Renaud, A et al. (1995) Effect of 5-HT1A receptor agonists and antagonists on canine cataplexy. J Pharmacol Exp Ther 272:1170-5
Reid, M S; Siegel, J M; Dement, W C et al. (1994) Cholinergic mechanisms in canine narcolepsy--II. Acetylcholine release in the pontine reticular formation is enhanced during cataplexy. Neuroscience 59:523-30
Reid, M S; Tafti, M; Geary, J N et al. (1994) Cholinergic mechanisms in canine narcolepsy--I. Modulation of cataplexy via local drug administration into the pontine reticular formation. Neuroscience 59:511-22
Mignot, E; Nishino, S; Sharp, L H et al. (1993) Heterozygosity at the canarc-1 locus can confer susceptibility for narcolepsy: induction of cataplexy in heterozygous asymptomatic dogs after administration of a combination of drugs acting on monoaminergic and cholinergic systems. J Neurosci 13:1057-64
Mignot, E; Wang, C; Rattazzi, C et al. (1991) Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment. Proc Natl Acad Sci U S A 88:3475-8
Miller, J D; Faull, K F; Bowersox, S S et al. (1990) CNS monoamines and their metabolites in canine narcolepsy: a replication study. Brain Res 509:169-71
Dean, R R; Kilduff, T S; Dement, W C et al. (1989) Narcolepsy without unique MHC class II antigen association: studies in the canine model. Hum Immunol 25:27-35
Bowersox, S S; Kilduff, T S; Faull, K F et al. (1987) Brain dopamine receptor levels elevated in canine narcolepsy. Brain Res 402:44-8
Kilduff, T S; Bowersox, S S; Kaitin, K I et al. (1986) Muscarinic cholinergic receptors and the canine model of narcolepsy. Sleep 9:102-6
Faull, K F; Zeller-DeAmicis, L C; Radde, L et al. (1986) Biogenic amine concentrations in the brains of normal and narcoleptic canines: current status. Sleep 9:107-10

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