Research article summary (published 7 Sep 2009):

Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers.

Full Abstract

Orexin A/hypocretin-1 (oxA/hcrt-1) is known to be a modulator of dopamine-dependent neuronal activity and behaviors. However, the role of this system in driving motivated behaviors remains poorly understood. Here, we show that orexin/hypocretin receptor-1 (ox/hcrt-1R) signaling is important for motivation for highly salient, positive reinforcement. Blockade of ox/hcrt-1R selectively reduced work to self-administer cocaine or high fat food pellets. Moreover, oxA/hcrt-1 strengthened presynaptic glutamatergic inputs to the ventral tegmental area (VTA) only in cocaine or high fat self-administering rats. Finally, oxA/hcrt-1-mediated excitatory synaptic transmission onto VTA neurons was not potentiated following an arousing, aversive stimulus, suggesting that oxA/hcrt-1-mediated glutamatergic synaptic transmission was potentiated selectively with highly salient positive reinforcers. These experiments provide evidence for a selective role of oxA/hcrt-1 signaling in motivation for highly salient reinforcers and may represent a unique opportunity to design novel therapies that selectively reduce excessive drive to consume positive reinforcers of high salience.

Author information

Author/s: Borgland, Stephanie L (SL); Chang, Shao-Ju (SJ); Bowers, M Scott (MS); Thompson, Jennifer L (JL); Vittoz, Nicole (N); Floresco, Stan B (SB); Chou, Jonathan (J); Chen, Billy T (BT); Bonci, Antonello (A);

Affiliation: Ernest Gallo Clinic and Research Center, Department of Neurology, , University of California, San Francisco, San Francisco, California 94110, USA. Borgland(-atsign-)interchange.ubc.ca

Grants: 1R01DA15096 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Sep; vol 29 (issue 36) : pp 11215-25

Dates: Created 2009/09/10; Completed 2009/09/28; Revised 2009/11/03;

PMID: 19741128, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Benzoxazoles - pharmacology Choice Behavior - drug effects; physiology Cocaine-Related Disorders - prevention & control Dietary Fats - administration & dosage; antagonists & inhibitors Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; physiology Male Motivation

Neural Pathways - drug effects; physiology Neuropeptides - antagonists & inhibitors; physiology Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled - antagonists & inhibitors; physiology Receptors, Neuropeptide - antagonists & inhibitors; physiology Reinforcement (Psychology) Urea - analogs & derivatives; pharmacology

Associated Chemicals: 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea (0) ; Benzoxazoles (0) ; Dietary Fats (0) ; Intracellular Signaling Peptides and Proteins (0) ; Neuropeptides (0) ; Receptors, G-Protein-Coupled (0) ; Receptors, Neuropeptide (0) ; orexin receptors (0) ; orexins (0) ; Urea (57-13-6)

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