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Review
. 2017:136:199-237.
doi: 10.1016/bs.irn.2017.06.006. Epub 2017 Aug 8.

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Jessica R Barson  1 , Sarah F Leibowitz  2
Affiliations
Review

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Jessica R Barson et al. Int Rev Neurobiol. 2017.

Abstract

The neuropeptide orexin/hypocretin (OX), while largely transcribed within the hypothalamus, is released throughout the brain to affect complex behaviors. Primarily through the hypothalamus itself, OX homeostatically regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, through extrahypothalamic limbic brain regions, OX promotes seeking and intake of rewarding substances of abuse, like palatable food, alcohol, nicotine, and cocaine. This neuropeptide, in turn, is stimulated by the intake of or early life exposure to these substances, forming a nonhomeostatic, positive feedback loop. The specific OX receptor involved in these behaviors, whether adaptive behavior or substance seeking and intake, is dependent on the particular brain region that contributes to them. Thus, we propose that, while the primary function of OX is to maintain arousal for the performance of adaptive behaviors, this neuropeptide system is readily co-opted by rewarding substances that involve positive feedback, ultimately promoting their abuse.

Keywords: Alcohol; Cocaine; Fat; Intake; Maternal behavior; Mating; Nicotine; Seeking; Sleep–wake; Sucrose.

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References

    1. Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450(7168):420–424. doi: 10.1038/nature06310. - DOI - PMC - PubMed
    1. Akiyama M, Yuasa T, Hayasaka N, Horikawa K, Sakurai T, Shibata S. Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice. Eur J Neurosci. 2004;20(11):3054–3062. doi: 10.1111/j.1460-9568.2004.03749.x. - DOI - PubMed
    1. Alcaraz-Iborra M, Carvajal F, Lerma-Cabrera JM, Valor LM, Cubero I. Binge-like consumption of caloric and non-caloric palatable substances in ad libitum-fed C57BL/6J mice: pharmacological and molecular evidence of orexin involvement. Behav Brain Res. 2014;272:93–99. doi: 10.1016/j.bbr.2014.06.049. - DOI - PubMed
    1. Anderson RI, Becker HC, Adams BL, Jesudason CD, Rorick-Kehn LM. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models. Front Neurosci. 2014;8:33. doi: 10.3389/fnins.2014.00033. - DOI - PMC - PubMed
    1. Archer ZA, Findlay PA, Rhind SM, Mercer JG, Adam CL. Orexin gene expression and regulation by photoperiod in the sheep hypothalamus. Regul Pept. 2002;104(1-3):41–45. - PubMed

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