Document Detail


Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity.
MedLine Citation:
PMID:  20338186     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Orexins (also named hypocretins) are recently discovered neuropeptides made exclusively in the hypothalamus. Recent studies have shown that orexin cells located specifically in lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. Administration of orexin has been shown to stimulate food consumption, and orexin signaling in VTA has been implicated in intake of high-fat food. In self-administration studies, the orexin 1 receptor antagonist SB-334867 (SB) attenuated operant responding for high-fat pellets, sucrose pellets and ethanol, but not cocaine, demonstrating that signaling at orexin receptors is necessary for reinforcement of specific rewards. The orexin system is also implicated in associations between rewards and relevant stimuli. For example, Fos expression in LH orexin neurons varied in proportion to conditioned place preference (CPP) for food, morphine, or cocaine. This Fos expression was altered accordingly for CPP administered during protracted abstinence from morphine or cocaine, when preference for natural rewards was decreased and drug preference was increased. Additionally, orexin has been shown to be involved in reward-stimulus associations in the self-administration paradigm, where SB attenuated cue-induced reinstatement of extinguished sucrose- or cocaine-seeking. Although the specific circuitry mediating the effects of orexin on food reward remains unknown, VTA seems likely to be a critical target for at least some of these orexin actions. Thus, recent studies have established a role for orexin in reward-based feeding, and further investigation is warranted for determining whether function/dysfunction of the orexin system may contribute to the overeating associated with obesity. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
Authors:
Angie M Cason; Rachel J Smith; Pouya Tahsili-Fahadan; David E Moorman; Gregory C Sartor; Gary Aston-Jones
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Publication Detail:
Type:  Journal Article; Review     Date:  2010-03-23
Journal Detail:
Title:  Physiology & behavior     Volume:  100     ISSN:  1873-507X     ISO Abbreviation:  Physiol. Behav.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-15     Completed Date:  2010-09-16     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0151504     Medline TA:  Physiol Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-28     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Addictive / metabolism*,  psychology*
Food Preferences
Humans
Hypothalamic Area, Lateral / metabolism
Intracellular Signaling Peptides and Proteins / metabolism*
Neuropeptides / metabolism*
Obesity / metabolism*
Orexin Receptors
Receptors, G-Protein-Coupled / antagonists & inhibitors
Receptors, Neuropeptide / antagonists & inhibitors
Reward*
Grant Support
ID/Acronym/Agency:
F32 DA023354-03/DA/NIDA NIH HHS; P50 DA015369/DA/NIDA NIH HHS; P50 DA015369-070007/DA/NIDA NIH HHS; R01 DA017289/DA/NIDA NIH HHS; R01 DA017289-06/DA/NIDA NIH HHS; R37 DA006214/DA/NIDA NIH HHS; R37 DA006214-21/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Orexin Receptors; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexins
Comments/Corrections

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