Document Detail


Role of orexin/hypocretin in conditioned sucrose-seeking in rats.
MedLine Citation:
PMID:  23096770     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. We reasoned that this system may be strongly engaged during periods of reward restriction, including food restriction.
OBJECTIVES: This study examined the involvement of the orexin (Orx) system in responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed versus food-restricted male subjects.
METHODS: Sprague-Dawley rats (n = 108) were trained to self-administer sucrose, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10-30 mg/kg) on fixed ratio (FR) or progressive ratio (PR) sucrose self-administration, as well as on cue-induced reinstatement of sucrose-seeking. Finally, expression of the immediate early gene c-fos in Orx neurons was examined after self-administration, late extinction or cue-induced reinstatement of sucrose seeking.
RESULTS: SB decreased lever responding (by about 1/3) and the number of reinforcers earned during FR, and less so during PR, schedules and decreased cue-induced reinstatement to sucrose-seeking to extinction levels, predominately in food-restricted rats. Additionally, Fos expression in Orx neurons in perifornical and dorsomedial hypothalamus was increased during extinction.
CONCLUSIONS: These results indicate that signaling at the OxR1 receptor is involved in pronounced sucrose reinforcement, and reinstatement of sucrose-seeking elicited by sucrose-paired cues, in food-restricted subjects. These findings lead us to conclude that conditioned activation of Orx neurons increases motivation for food reward during food restriction.
Authors:
Angie M Cason; Gary Aston-Jones
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-25
Journal Detail:
Title:  Psychopharmacology     Volume:  226     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-13     Completed Date:  2013-07-30     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  155-65     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Behavior, Animal / drug effects*
Benzoxazoles / pharmacology
Conditioning, Operant / drug effects
Drug-Seeking Behavior / drug effects*
Extinction, Psychological / drug effects
Food Deprivation
Immunohistochemistry
Intracellular Signaling Peptides and Proteins / metabolism*
Male
Neurons / drug effects,  metabolism
Neuropeptides / metabolism*
Orexin Receptors
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled / antagonists & inhibitors
Receptors, Neuropeptide / antagonists & inhibitors
Reinforcement Schedule*
Reward*
Self Administration
Sucrose / administration & dosage*
Urea / analogs & derivatives,  pharmacology
Grant Support
ID/Acronym/Agency:
F32 DA023354/DA/NIDA NIH HHS; F32 DA023354/DA/NIDA NIH HHS; R01 DA017289/DA/NIDA NIH HHS; R01 DA017289/DA/NIDA NIH HHS; R37 DA006214/DA/NIDA NIH HHS; R37 DA06214/DA/NIDA NIH HHS
Chemical
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/Orexin Receptors; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexins; 57-50-1/Sucrose; 8W8T17847W/Urea; E78ZFF4KQ0/Reward
Comments/Corrections

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