This project will address the problem of narcolepsy by conducting research on an animal model of the illness. The model consists of Doberman pinschers in which the sleep disorder is genetically transmitted by an autosomal recessive gene. Preliminary neurochemical evidence supports the hypothesis that a neurochemical defect is involved. We will pursue further elucidation of the pathological mechanisms in canine narcolepsy by carrying out studies in three areas. We will conduct regional assays of biogenic amines and their metabolites as well as measurement of binding sites and binding properties of dopaminergic, cholinergic, serotonergic, and adrenergic receptors. Other neurochemical studies will involve push-pull cannula approaches with assay of neurotransmitters and metabolites in perfusage. We also propose functional neuroanatomical mapping of cataplexy and REM sleep by 2-deoxyglucose techniques. Finally, we will investigate the neurophysiological substrates of narcolepsy be recording discharge patterns of single units in specific brainstem areas related to REM sleep control.
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| Guilleminault, C; Mignot, E; Grumet, F C (1989) Familial patterns of narcolepsy. Lancet 2:1376-9 |
| Mignot, E; Guilleminault, C; Bowersox, S et al. (1988) Role of central alpha-1 adrenoceptors in canine narcolepsy. J Clin Invest 82:885-94 |
| Mignot, E; Guilleminault, C; Bowersox, S et al. (1988) Effect of alpha 1-adrenoceptors blockade with prazosin in canine narcolepsy. Brain Res 444:184-8 |
| 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 |
| Bowersox, S S; Kilduff, T S; Kaitin, K I et al. (1986) Brain benzodiazepine receptor characteristics in canine narcolepsy. Sleep 9:111-5 |
| Kaitin, K I; Kilduff, T S; Dement, W C (1986) Sleep fragmentation in canine narcolepsy. Sleep 9:116-9 |
| Kaitin, K I; Kilduff, T S; Dement, W C (1986) Evidence for excessive sleepiness in canine narcoleptics. Electroencephalogr Clin Neurophysiol 64:447-54 |
