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Encyclopedia of Signaling Molecules pp 3665–3671Cite as

Orexin Receptor-1 (OX1R)

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Synonyms

Hypocretin (orexin) receptor 1; Ox1r; Ox-1-R; Ox1-R

Historical Background

Orexin or hypocretin; a peptide that resembles the molecular structure of the gastric peptide secretin, was discovered in 1996 by two independent groups of researchers. One group named it orexin after the Greek word orexis which means “appetite,” while the other group named it hypocretin since it was synthesized in the hypothalamus and resembles secretin (Sakurai et al. 1998). Both the nomenclatures for orexins are currently in use. We would adhere to “orexin” for references to the peptides in this article.

These hypothalamic peptides are produced by orexin neurons in the dorsomedial (DMH), lateral (LH), and perifornical hypothalamic areas (PFA) (Sakurai et al. 1998). Since these areas of the hypothalamus are involved in arousal, sleep-wake cycle, thermoregulation, feeding and appetite, the function of orexins is implicated in the regulation of these behaviors. Furthermore, studies have shown that...

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References

  • Abbas MG, Shoji H, Soya S, Hondo M, Miyakawa T, Sakurai T. Comprehensive behavioral analysis of male Ox1r (−/−) mice showed implication of orexin receptor-1 in mood, anxiety, and social behavior. Front Behav Neurosci. 2015;9:324. doi:10.3389/fnbeh.2015.00324.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bonaventure P, Yun S, Johnson PL, Shekhar A, Fitz SD, Shireman BT, et al. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects. J Pharmacol Exp Ther. 2015;352:590–601. doi:10.1124/jpet.114.220392.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brodnik ZD, Bernstein DL, Prince CD, Espana RA. Hypocretin receptor 1 blockade preferentially reduces high effort responding for cocaine without promoting sleep. Behav Brain Res. 2015;291:377–84. doi:10.1016/j.bbr.2015.05.051.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brown RM, Kim AK, Khoo SY, Kim JH, Jupp B, Lawrence AJ. Orexin-1 receptor signalling in the prelimbic cortex and ventral tegmental area regulates cue-induced reinstatement of ethanol-seeking in iP rats. Addict Biol. 2016;21:603–12. doi:10.1111/adb.12251.

    Article  PubMed  CAS  Google Scholar 

  • Cole S, Mayer HS, Petrovich GD. Orexin/hypocretin-1 receptor antagonism selectively reduces cue-induced feeding in sated rats and recruits medial prefrontal cortex and thalamus. Sci Rep. 2015;5:16143. doi:10.1038/srep16143.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ebrahim IO, Howard RS, Kopelman MD, Sharief MK, Williams AJ. The hypocretin/orexin system. J R Soc Med. 2002;95:227–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Haynes AC, Chapman H, Taylor C, Moore GB, Cawthorne MA, Tadayyon M, et al. Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. Regul Pept. 2002;104:153–9.

    Article  PubMed  CAS  Google Scholar 

  • Haynes AC, Jackson B, Chapman H, Tadayyon M, Johns A, Porter RA, et al. A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul Pept. 2000;96:45–51.

    Article  PubMed  CAS  Google Scholar 

  • Heidari-Oranjaghi N, Azhdari-Zarmehri H, Erami E, Haghparast A. Antagonism of orexin-1 receptors attenuates swim- and restraint stress-induced antinociceptive behaviors in formalin test. Pharmacol Biochem Behav. 2012;103:299–307. doi:10.1016/j.pbb.2012.08.007.

    Article  PubMed  CAS  Google Scholar 

  • Keefer SE, Cole S, Petrovich GD. Orexin/hypocretin receptor 1 signaling mediates Pavlovian cue-food conditioning and extinction. Physiol Behav. 2016;162:27–36. doi:10.1016/j.physbeh.2016.02.042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B. The orexin system regulates alcohol-seeking in rats. Br J Pharmacol. 2006;148:752–9. doi:10.1038/sj.bjp.0706789.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee HJ, Chang LY, Ho YC, Teng SF, Hwang LL, Mackie K, et al. Stress induces analgesia via orexin 1 receptor-initiated endocannabinoid/CB1 signaling in the mouse periaqueductal gray. Neuropharmacology. 2016;105:577–86. doi:10.1016/j.neuropharm.2016.02.018.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lopez M, Seoane L, Garcia MC, Lago F, Casanueva FF, Senaris R, et al. Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus. Biochem Biophys Res Commun. 2000;269:41–5. doi:10.1006/bbrc.2000.2245.

    Article  PubMed  CAS  Google Scholar 

  • Lopez MF, Moorman DE, Aston-Jones G, Becker HC. The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice. Brain Res. 2016;1636:74–80. doi:10.1016/j.brainres.2016.01.049.

    Article  CAS  Google Scholar 

  • Martin-Fardon R, Weiss F. Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking: comparison with natural reward seeking. NeuroReport. 2014;25:485–8. doi:10.1097/wnr.0000000000000120.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moorman DE, Aston-Jones G. Orexin-1 receptor antagonism decreases ethanol consumption and preference selectively in high-ethanol-preferring Sprague–Dawley rats. Alcohol. 2009;43:379–86. doi:10.1016/j.alcohol.2009.07.002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Piccoli L, Micioni Di Bonaventura MV, Cifani C, Costantini VJ, Massagrande M, Montanari D, et al. Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol. 2012;37:1999–2011. doi:10.1038/npp.2012.48.

    Article  CAS  Google Scholar 

  • Prince CD, Rau AR, Yorgason JT, España RA. Hypocretin/orexin regulation of dopamine signaling and cocaine self-administration is mediated predominantly by hypocretin receptor 1. ACS Chem Neurosci. 2015;6:138–46. doi:10.1021/cn500246j.

    Article  PubMed  CAS  Google Scholar 

  • Richards JK, Simms JA, Steensland P, Taha SA, Borgland SL, Bonci A, et al. Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats. Psychopharmacology (Berl). 2008;199:109–17. doi:10.1007/s00213-008-1136-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Risco S, Mediavilla C. Orexin-1 receptor antagonist in central nucleus of the amygdala attenuates the acquisition of flavor-taste preference in rats. Pharmacol Biochem Behav. 2014;126:7–12. doi:10.1016/j.pbb.2014.09.002.

    Article  PubMed  CAS  Google Scholar 

  • Rodgers RJ, Halford JC, Nunes de Souza RL, Canto de Souza AL, Piper DC, Arch JR, et al. SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats. Eur J Neurosci. 2001;13:1444–52.

    Article  PubMed  CAS  Google Scholar 

  • Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573–85.

    Article  PubMed  CAS  Google Scholar 

  • Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science (New York, NY). 2003;301:805–809. doi:10.1126/science.1083328.

    Article  PubMed  CAS  Google Scholar 

  • Sharf R, Sarhan M, Brayton CE, Guarnieri DJ, Taylor JR, DiLeone RJ. Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement. Biol Psychiatry. 2010;67:753–60. doi:10.1016/j.biopsych.2009.12.035.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Smith RJ, See RE, Aston-Jones G. Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking. Eur J Neurosci. 2009;30:493–503. doi:10.1111/j.1460-9568.2009.06844.x.

    Article  PubMed  PubMed Central  Google Scholar 

  • Soya S, Shoji H, Hasegawa E, Hondo M, Miyakawa T, Yanagisawa M, et al. Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation. J Neurosci. 2013;33:14549–57. doi:10.1523/jneurosci.1130-13.2013.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Terrill SJ, Hyde K, Kay K, Greene HE, Maske CB, Knierim AE, et al. Ventral Tegmental Area orexin 1 receptors promote palatable food intake and oppose post-ingestive negative feedback. Am J Physiol Regul Integr Comp Physiol. 2016:ajpregu.00097.2016. doi:10.1152/ajpregu.00097.2016.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tsujino N, Sakurai T. Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev. 2009;61:162–76. doi:10.1124/pr.109.001321.

    Article  PubMed  CAS  Google Scholar 

  • Zhao X, Zhang R, Tang S, Ren Y, Yang W, Liu X, et al. Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis. Peptides. 2014;54:140–7. doi:10.1016/j.peptides.2013.11.019.

    Article  PubMed  CAS  Google Scholar 

  • Zhou L, Smith RJ, Do PH, Aston-Jones G, See RE. Repeated orexin 1 receptor antagonism effects on cocaine seeking in rats. Neuropharmacology. 2012;63:1201–7. doi:10.1016/j.neuropharm.2012.07.044.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, Australia

    Omkar L. Patkar

  2. Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia

    Arnauld Belmer

  3. Queensland University of Technology (QUT), Brisbane, QLD, Australia

    Selena E. Bartlett

Authors
  1. Omkar L. Patkar
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  2. Arnauld Belmer
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  3. Selena E. Bartlett
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Corresponding author

Correspondence to Omkar L. Patkar .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Patkar, O.L., Belmer, A., Bartlett, S.E. (2018). Orexin Receptor-1 (OX1R). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101540

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