Document Detail

Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement.
MedLine Citation:
PMID:  20189166     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Orexin (hypocretin) signaling is implicated in drug addiction and reward, but its role in feeding and food-motivated behavior remains unclear.
METHODS: We investigated orexin's contribution to food-reinforced instrumental responding using an orexin 1 receptor (Ox1r) antagonist, orexin -/- (OKO) and littermate wildtype (WT) mice, and RNAi-mediated knockdown of orexin. C57BL/6J (n = 76) and OKO (n = 39) mice were trained to nose poke for food under a variable ratio schedule of reinforcement. After responding stabilized, a progressive ratio schedule was initiated to evaluate motivation to obtain food reinforcement.
RESULTS: Blockade of Ox1r in C57BL/6J mice impaired performance under both the variable ratio and progressive ratio schedules of reinforcement, indicating impaired motivational processes. In contrast, OKO mice initially demonstrated a delay in acquisition but eventually achieved levels of responding similar to those observed in WT animals. Moreover, OKO mice did not differ from WT mice under a progressive ratio schedule, indicating delayed learning processes but no motivational impairments. Considering the differences between pharmacologic blockade of Ox1r and the OKO mice, animals with RNAi mediated knockdown of orexin were then generated and analyzed to eliminate possible developmental effects of missing orexin. Orexin gene knockdown in the lateral hypothalamus in C57BL/6J mice resulted in blunted performance under both the variable ratio and progressive ratio schedules, resembling data obtained following Ox1r antagonism.
CONCLUSIONS: The behavior seen in OKO mice likely reflects developmental compensation often seen in mutant animals. These data suggest that activation of the Ox1r is a necessary component of food-reinforced responding, motivation, or both in normal mice.
Ruth Sharf; Maysa Sarhan; Catherine E Brayton; Douglas J Guarnieri; Jane R Taylor; Ralph J DiLeone
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-26
Journal Detail:
Title:  Biological psychiatry     Volume:  67     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-05     Completed Date:  2010-06-17     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  753-60     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Benzoxazoles / pharmacology
Conditioning, Operant / physiology*
Data Interpretation, Statistical
Hypothalamic Area, Lateral / physiology
Intracellular Signaling Peptides and Proteins / physiology*
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / drug effects
Neuropeptides / physiology*
Orexin Receptors
RNA Interference
Receptors, Neuropeptide / genetics*,  physiology*
Reinforcement (Psychology)
Reinforcement Schedule
Urea / analogs & derivatives,  pharmacology
Viruses / genetics
Grant Support
F32DA023739/DA/NIDA NIH HHS; P50 MH066172/MH/NIMH NIH HHS; P50 MH066172-080003/MH/NIMH NIH HHS; R01 DA011717/DA/NIDA NIH HHS; R01 DA015222/DA/NIDA NIH HHS; R01 DA017676/DA/NIDA NIH HHS; R01 DA017676-05/DA/NIDA NIH HHS; R01DA017676/DA/NIDA NIH HHS; RL1AA017537/AA/NIAAA NIH HHS
Reg. No./Substance:
0/1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; 0/Benzoxazoles; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/OX1 protein, mouse; 0/Orexin Receptors; 0/Receptors, Neuropeptide; 0/orexins; 8W8T17847W/Urea

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