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The Hypocretin/Orexin System: Implications for Drug Reward and Relapse

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Abstract

Hypocretins (also known as orexins) are hypothalamic neuropeptides involved in the regulation of sleep/wake states and feeding behavior. Recent studies have also demonstrated an important role for the hypocretin/orexin system in the addictive properties of drugs of abuse, consistent with the reciprocal innervations between hypocretin neurons and brain areas involved in reward processing. This system participates in the primary reinforcing effects of opioids, nicotine, and alcohol. Hypocretins are also involved in the neurobiological mechanisms underlying relapse to drug-seeking behavior induced by drug-related environmental stimuli and stress, as mainly described in the case of psychostimulants. Based on these preclinical studies, the use of selective ligands targeting hypocretin receptors could represent a new therapeutical strategy for the treatment of substance abuse disorders. In this review, we discuss and update the current knowledge about the participation of the hypocretin system in drug addiction and the possible neurobiological mechanisms involved in these processes regulated by hypocretin transmission.

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Acknowledgments

This work was supported by the Instituto de Salud Carlos III grants #PI07/0559, #PI10/00316, and #RD06/001/001 (RTA-RETICS), by the Spanish Ministry of Science and Technology (Consolider-C, #SAF2007-64062), the Catalan Government (SGR2009-00731), and by the Catalan Institution for Research and Advanced Studies (ICREA Academia program). A Plaza-Zabala is a recipient of a predoctoral fellowship from the Spanish Ministry of Education.

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The authors declare that they have no conflict of interest.

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  1. Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, University Pompeu Fabra, PRBB, C/Doctor Aiguader 88, 08003, Barcelona, Spain

    Ainhoa Plaza-Zabala, Rafael Maldonado & Fernando Berrendero

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  1. Ainhoa Plaza-Zabala
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  2. Rafael Maldonado
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  3. Fernando Berrendero
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Correspondence to Fernando Berrendero.

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Plaza-Zabala, A., Maldonado, R. & Berrendero, F. The Hypocretin/Orexin System: Implications for Drug Reward and Relapse. Mol Neurobiol 45, 424–439 (2012). https://doi.org/10.1007/s12035-012-8255-z

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