The role of hypocretins (Orexins) in sleep regulation and narcolepsy

Shahrad Taheri, Jamie M. Zeitzer, Emmanuel Mignot

Research output: Contribution to journalReview article

270 Citations (Scopus)


The hypocretins (orexins) are two novel neuropeptides (Hcrt-1 and Hcrt-2), derived from the same precursor gene, that are synthesized by neurons located exclusively in the lateral, posterior, and perifomical hypothalamus. Hypocretincontaining neurons have widespread projections throughout the CNS with particularly dense excitatory projections to monoaminergic centers such as the noradrenergic locus coeruleus, histaminergic tuberomammillary nucleus, serotoninergic raphe nucleus, and dopaminergic ventral tegrnental area. The hypocretins were originally believed to be primarily important in the regulation of appetite; however, a major function emerging from research on these neuropeptides is the regulation of sleep and wakefulness. Deficiency in hypocretin neurotransmission results in the sleep disorder narcolepsy in mice, dogs, and humans. The hypocretins are also uniquely positioned to link sleep, appetite, and neuroendocrine control. The aim of this review is to describe and discuss the current knowledge regarding the hypocretin neurotransmitter system in narcolepsy and normal sleep.

Original languageEnglish
Pages (from-to)283-313
Number of pages31
JournalAnnual Review of Neuroscience
Publication statusPublished - 2002
Externally publishedYes



  • Appetite
  • Arousal
  • Energy expenditure
  • Lateral hypothalamus
  • Neuroendocfine

ASJC Scopus subject areas

  • Neuroscience(all)

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