Orexin/hypocretin role in reward: implications for opioid and other addictions

Baimel, Corey, Bartlett, Selena E., Chiou, Lih-Chu, Lawrence, Andrew J, Muschamp, John W, Patkar, Omkar, Tung, Li-Wei, & Borgland, Stephanie L (2015) Orexin/hypocretin role in reward: implications for opioid and other addictions. British Journal of Pharmacology, 172(2), pp. 334-348.

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Abstract

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

Impact and interest:

23 citations in Scopus
21 citations in Web of Science®
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ID Code: 80178
Item Type: Journal Article
Refereed: Yes
Keywords: orexin, hypocretin, dynorphin, morphine, addiction, dopamine, VTA
DOI: 10.1111/bph.12639
ISSN: 00071188
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NEUROSCIENCES (110900)
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright © 1999-2014 John Wiley & Sons, Inc
Deposited On: 16 Jan 2015 04:54
Last Modified: 19 Jan 2015 04:29

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