The Hypocretin/Orexin System

Sutcliffe J.G. , de Lecea L. The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding. J Neurosci Res 2000; 62: 161–8

de Lecea L. , Kilduff T.S. , Peyron C. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 1998; 95: 322–7

Sakurai T. , Amemiya A. , Ishii M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G-protein coupled receptors that regulate feeding behaviour. Cell 1998; 92: 573–5

Gautvik K.M. , de Lecea L. , Gautvik V.T. Overview of the most prevalent hypothalamus-specific mRNAs, as identified by directional tag PCR subtraction. Proc Natl Acad Sci USA 1996; 93: 8733–8

Peyron C. Distribution of immunoreactive neurons and fibers for a hypothalamic neuropeptide precursor related to secretin. Soc Neurosci Abstr 1997; 23: 2032

Sutcliffe JG. Two novel hypothalamic peptides related to secretin derived from a single neuropeptide precursor. Soc Neurosci Abstr 1997; 23: 2032

Kilduff T.S. , Peyron C. The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. TINS 2000; 23: 359–64

Trivedi P. , Yu H. , MacNeil D.J. , Van der Ploeg L.H. , Guan XM. Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 1998; 438: 71–5

Chicurel M. The sandman's secrets. Nature 2000; 407: 554–6

Mignot E. Perspectives in narcolepsy and hypocretin (orexin) research. Sleep Med 2000; 1: 87–90

Peyron C. , Tighe D.K. , Van den Pol A.N. Neurones containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998; 23: 9996–10015

Peyron C. , Faraco J. , Rogers W. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 2000; 6: 991–7

Thannickal T.C. , Moore R.Y. , Nienhuis R. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27: 469–74

van den Pol AN. Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci 1999; 19: 3171–82

Horvath T.L. , Peyron C. , Diane S. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J Comp Neurol 1999; 415: 145–59

Ida T. , Nakahara K. , Kuroiwa T. Both corticotrophin releasing factor and neuropeptide Y are involved in the effect of orexin (hypocretin) on the food intake in rats. Neurosci Lett 2000; 293: 119–22

van den Pol A.N. , Gao X.B. , Obrietan K. , Kilduff T.S. , Belousov AB. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurones by a new hypothalamic peptide, hypocretin/orexin. J Neurosci 1998; 18: 7962–71

John J. , Wu M.F. , Kodana T. , Siegel JM. Hypocretin-1 (orexin-A) produced changes in glutamate and GABA release: an in vivo microdialysis study [Abstract]. Sleep 2001; 24(suppl): A20

Edwards C.M. , Abusnana S. , Sunter D. , Murphy K.G. , Ghaten M.A. , Bloom SR. The effect of orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin. J Endocrinol 1999; 160: R7–12

Haynes A.C. , Jackson B. , Overend P. Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat. Peptides 1999; 20: 1099–105

Moriguchi T. , Sakurai T. , Nambu T. , Yanagisawa M. , Goto K. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neurosci Lett 1999; 264: 101–4

Kuru M. , Ueta Y. , Serino R. Centrally administered orexin-hypocretin activates HPA axis in rats. Neuroreport 2000; 11: 1977–80

Kirchgessner A.L. , Liu M. Orexin synthesis and response in the gut. Neuron 1999; 24: 941–51

Samson W.K. , Gosnell B. , Chang J.K. , Resch Z.T. , Murphy TC. Cardiovascular regulatory actions of the hypocretins in brain. Brain Res 1999; 831: 248–53

Ida T. , Nakahara K. , Katayama T. , Murakami N. , Nakazato M. Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptides, orexin and neuropeptide Y, on the various behavioural activities of rats. Brain Res 1999; 821: 526–9

Samson W.K. , Resch ZT. The hypocretin/orexin story. Trends Endocrinol Metab 2000; 11: 257–62

Krahn L.E. , Black J.L. , Silber MH. Narcolepsy: new understanding of irresistible sleep. Mayo Clin Proc 2001; 76: 185–94

Lin L. , Farace J. , Li R. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999; 98: 365–76

Chemelli R.M. , Willie J.T. , Sinton C.M. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98: 437–51

Kisanuki Y.Y. , Chemelli R.M. , Tokita S. Behavioural and polysomnographic characterization of orexin-1 receptor and orexin-2 receptor double knockout mice [Abstract]. Sleep 2001; 24(suppl): A22

Kisanuki Y.Y. , Chemelli RM. The role of orexin receptor type-1 (OX1R) in the regulation of sleep [Abstract]. Sleep 2000; 23(suppl): A91

Takita S. , Chemelli R.M. , Willie J.T. , Yanagisawa M. Behavioural characterisation of orexin-2 receptor (OX2R) knockout mice [Abstract]. Sleep 2001; 24(suppl): A20

John J. , Wu M.F. , Siegel JM. Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs. Sleep Res Online 2000; 3: 23–8

Nishino S. , Ripley B. , Overeem S. , Lammers G.J. , Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000; 355: 39–40

Kanbayashi T. , Yano T. , Ishiguro H. Hypocretin (orexin) levels in human lumbar CSF in different age groups [Abstract]. Sleep 2001; 24(suppl): A330

Ripley B. , Overeem S. , Fujiki N. CSF hypocretin levels in various neurological conditions: low levels in narcolepsy and Guillain Barré Syndrome [Abstract]. Sleep 2001; 24(suppl): A322

Kanbayashi T. , Ishiguro H. , Yano T. Hypocretin/orexin concentrations are low in patients with Guillain Barré syndrome [Abstract]. Sleep 2001; 24(suppl): A331–2

Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 1998; 59: 11–14

van den Pol AN. Narcolepsy: a neurodegenerative disease of the hypocretin system? Neuron 2000; 27: 415–18

Bunney W.E. , Davis JM. Noradrenaline in depressive reactions. A review. Arch Gen Psychiatry 1965; 13: 483–94

Coppen A. The biochemistry of affective disorders. Br J Psychiatry 1967; 113: 1237–64

Miller H.L. , Delgado P.L. , Salomon R.M. Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Arch Gen Psychiatry 1996; 53: 117–28

Gold P.W. , Chrousos G. , Kellner C. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am J Psychiatry 1984; 141: 619–27

Gold P.W. , Loriaux D.L. , Roy A. Responses to corticotropin-releasing hormone in the hypercorticolism of depression and Cushing's disease. Pathophysiologic and diagnostic implications. N Engl J Med 1986; 314: 1329–35

Holsboer F. , Van Bardeleben U. , Gerken A. , Stalla G.R. , Muller OA. Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor in depression. N Engl J Med 1984; 311: 1127

Kramer M.S. , Cutler N. , Feighner J. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 1998; 281: 1640–5

Wong M-L , Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci 2001; 2: 343–51

Zobel A.W. , Nickel T. , Kunzel M.E. Effects of high-affinity corticotropin releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res 2000; 34: 171–81

Melberg A. , Ripley B. , Lin L. , Hetta J. , Mignot E. , Nishino S. Hypocretin deficiency in familial symptomatic narcolepsy. Ann Neurol 2001; 49: 136–7

Salin-Pascual RJ. The role of the hypothalamic neuropeptides hypocretin/orexin the sleep-wake cycle. Isr Med Assoc J 2001; 3: 144–6

Scammell T.E. , Estabrooke I.V. , McCarthy M.T. Hypothalamic arousal regions are activated during Modafinil-induced wakefulness. J Neurosci 2000; 20: 8620–8