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The Journal of Neuroscience, July 1, 2002, 22(13):5282-5286

BRIEF COMMUNICATION
Release of Hypocretin (Orexin) during Waking and Sleep States

Lyudmila I. Kiyashchenko^{1, 2, 3, *}, Boris Y. Mileykovskiy^{1, 2, 3, *}, Nigel Maidment¹, Hoa A. Lam¹, Ming-Fung Wu^{1, 2}, Joshi John^{1, 2}, John Peever^{1, 2}, and Jerome M. Siegel^{1, 2}

¹ Department of Psychiatry and Biobehavioral Sciences and Brain Research Institute, University of California Los Angeles School of Medicine, and ² Veterans Administration of Greater Los Angeles Healthcare System-Sepulveda, North Hills, California 91343, and ³ Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science, St. Petersburg, 194223, Russia

Hypocretin (Hcrt or orexin) somas are located in the hypothalamus and project widely to forebrain and brainstem regions, densely innervating monoaminergic and cholinergic cells. Loss of Hcrt function results in the sleep disorder narcolepsy. However, the normal pattern of Hcrt release across the sleep-wake cycle is unknown. We monitored Hcrt-1 release in the basal forebrain, perifornical hypothalamus, and locus ceruleus (LC) across the sleep-wake cycle using microdialysis in freely moving cats and a sensitive solid phase radioimmunoassay. We found that the peptide concentration in dialysates from the hypothalamus was significantly higher during active waking (AW) than during slow-wave sleep (SWS). Moreover, Hcrt-1 release was significantly higher during rapid eye movement (REM) sleep than during SWS in the hypothalamus and basal forebrain. We did not detect a significant difference in release across sleep-waking states in the LC, perhaps because recovered levels of the peptide were lower at this site. Because there was a trend toward higher levels of Hcrt-1 release during AW compared with quiet waking (QW) in our 10 min dialysis samples, we compared Hcrt-1 levels in CSF in 2 hr AW and QW periods. Hcrt-1 release into CSF was 67% higher during AW than during QW. Elevated levels of Hcrt during REM sleep and AW are consistent with a role for Hcrt in the central programming of motor activity.

Key words: hypocretin; orexin; microdialysis; sleep-waking cycle; motor activity; cataplexy

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^* L.I.K. and B.Y.M., contributed equally to this study.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22135282-05$05.00/0

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