Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement.

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 of dogs during a variety of behaviors. We found that 48 h without food (24 h beyond normal 24-h fasting period) produced no significant change in Hcrt-1 levels nor did feeding after the deprivation. In contrast, 24 h of sleep deprivation produced on average a 70% increase in Hcrt-1 level compared with baseline levels. The amount of increase was correlated with the level of motor activity during the sleep-deprivation procedure. A 2-h 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.