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The orexin system and nicotine addiction: preclinical insights


The orexin system and nicotine addiction: preclinical insights

Khoo, Shaun ORCID: https://orcid.org/0000-0002-0972-3788, McNally, Gavan ORCID: https://orcid.org/0000-0001-9061-6463 and Clemens, Kelly ORCID: https://orcid.org/0000-0003-2709-218X (2019) The orexin system and nicotine addiction: preclinical insights. In: The Neuroscience of Nicotine: Mechanisms and Treatment. Academic Press, London, pp. 509-517. ISBN 9780128130353

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Khoo-etal-2019-OrexinsNeuroscienceNicotine.pdf - Accepted Version
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Current pharmacotherapies for smoking have only modest efficacy with failure rates of up to 90%. One potential target for new pharmacotherapies is the orexin/hypocretin system, a hypothalamic neuropeptide system involved in arousal, appetite and reward. The orexin system has been suggested as a potential therapeutic target for nicotine addiction because there are orexin/nicotine interactions following both acute and chronic nicotine administration, preclinical findings in animal models of nicotine addiction and some correlational studies in humans. Acute orexin administration activates cholinergic neurons and acute nicotine administration activates orexin neurons, while chronic nicotine causes an upregulation in orexin peptides and receptors while decreasing the availability of orexin binding sites. A small number of preclinical studies in animal models of nicotine addiction have found effects of orexin antagonists in reducing nicotine self-administration and/or reinstatement behaviour, but results are not always entirely consistent between studies. A few human studies have found negative correlations between orexin levels and measures of nicotine craving in humans, or genetic associations between hypocretin receptor polymorphism and nicotine dependence. However, further research is required to reconcile discrepancies in the preclinical literature and to understand the role of the orexin system in nicotine dependence before clinical trials can be proposed.

Divisions:Concordia University > Research Units > Centre for Studies in Behavioural Neurobiology
Item Type:Book Section
Authors:Khoo, Shaun and McNally, Gavan and Clemens, Kelly
Date:22 March 2019
Identification Number:978-0-12-813035-3
Digital Object Identifier (DOI):10.1016/B978-0-12-813035-3.00061-7
Keywords:nicotine, orexin, hypocretin, self-administration, reinstatement, SB-334867, TCS 1102
ID Code:983393
Deposited On:08 Apr 2019 18:59
Last Modified:08 Apr 2019 18:59
Related URLs:
Additional Information:This accepted manuscript version is made available for non-commercial use in the author’s institutional repository in accordance with the copyright agreement signed with the publisher. Copyright © 2019 Elsevier Inc.


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