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Hypocretin\u20101 and \u20102 (also called orexin\u2010A and \u2010B) are newly discovered neuropeptides processed from a common precursor, preprohypocretin. Hypocretin\u2010containing cells are located exclusively in the lateral hypothalamus, with widespread projections to the entire neuroaxis. Two known receptors, Hcrtr1 and Hcrtr2, have been reported. The functional significance of the hypocretin system is rapidly emerging in both animals and humans. Hypocretin abnormalities cause narcolepsy in dogs, human and mice. The role of the hypocretin system in normal sleep regulation is more uncertain. We believe hypocretin cells drive cholinergic and monoaminergic activity across the sleep cycle. Input from the suprachiasmatic nucleus to hypocretin\u2010containing neurons may explain the occurrence of clock\u2010dependent alertness. Other functions are suggested by pharmacological and neurochemical experiments. These include regulation of food intake, neuroendocrine function, autonomic nervous system activity and energy balance. <jats:italic>BioEssays<\/jats:italic> 23:397\u2013408, 2001. \u00a9 2001 John Wiley &amp; Sons, Inc.<\/jats:p>","DOI":"10.1002\/bies.1058","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T20:13:04Z","timestamp":1030306384000},"page":"397-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Hypocretin\/orexin, sleep and 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