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Am J Physiol Regul Integr Comp Physiol (July 25, 2002). doi:10.1152/ajpregu.00207.2002
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Articles in PresS, published online ahead of print July 25, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00207.2002
Submitted on April 10, 2002
Accepted on July 19, 2002

Hypocretin/orexin release in normal and narcoleptic dogs: Effects of food deprivation, eating, sleep deprivation and movement

Ming-Fung Wu1*, Joshi John1, Nigel Maidment2, Hoa A Lam2, and Jerome M Siegel1

1 Neurobiology Research, VA GLAHS-Sepulveda, North Hills, CA, USA; Department of Psychiatry, UCLA, Los Angeles, CA, USA
2 Department of Psychiatry, UCLA, Los Angeles, CA, USA; Brain Research Institute, UCLA, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: mfw{at}ucla.edu.

Hypocretins (orexins) are recently discovered hypothalamic neuropeptides that have been implicated in the etiology of narcolepsy. The normal behavioral functions of these peptides are unclear, although a role in feeding has been suggested. We measured hypocretin-1 (Hcrt-1) in the cerebrospinal fluid (CSF) of dogs during a variety of behaviors. We found that 48 hours without food (24 hours beyond normal 24-h fasting period) produced no significant change in Hcrt-1 levels, nor did feeding after the deprivation. In contrast, 24 hours of sleep deprivation produced on average a 70% increase in Hcrt-1 level compared to baseline levels. The amount of increase was correlated with the level of motor activity during the sleep deprivation procedure. A 2-hour period of exercise in the same dogs produced a 57% increase in Hcrt-1 levels relative to quiet waking levels, with the magnitude of the increase being highly correlated with the level of motor activity. The strong correlation between motor activity and Hcrt-1 release may explain some of the previously reported behavioral, physiological and pathological phenomena ascribed to the Hcrt system.




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