Document Detail

Obese OLETF rats exhibit increased operant performance for palatable sucrose solutions and differential sensitivity to D2 receptor antagonism.
MedLine Citation:
PMID:  17804583     Owner:  NLM     Status:  MEDLINE    
CCK-1-receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and exhibit a greater preference for sucrose compared with lean controls [Long-Evans Tokushima Otsuka (LETO)]. To directly assess motivation to work for sucrose reward in this model of obesity and type 2 diabetes, we examined the operant performance of OLETF rats at nondiabetic and prediabetic stages (14 and 24 wk of age, respectively) on fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. To evaluate the involvement of dopamine systems, the effects of the D1 receptor antagonist SCH23390 (100 and 200 nmol/kg ip) and the D2 receptor antagonist raclopride (200 and 400 nmol/kg ip), were also tested on PR responding for sucrose. Compared with age-matched LETO rats, 14-wk-old OLETF rats emitted more licks on the "active" empty spout operant on the FR-10 schedule of reinforcement to obtain 0.01 M and 0.3 M sucrose and completed higher ratio requirements on the PR schedule to gain access to 0.3 M and 1.0 M sucrose. At 24 wk, this effect was limited to 1.0 M sucrose. Both antagonists were potent in reducing operant responding to 0.3 M sucrose in both strains at both ages, and there was no strain effect to SCH23390 at either age. OLETF rats, on the other hand, showed an increased sensitivity to the higher dose of raclopride, resulting in reduced responding to sucrose reinforcement at 24 wk. Taken together, these findings provide the first direct evidence for an increased motivation for sucrose reward in the OLETF rats and suggest altered D2 receptor regulation with the progression of obesity and prediabetes.
Andras Hajnal; Nikhil K Acharya; Patricia S Grigson; Mihai Covasa; Robert C Twining
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-09-05
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  293     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2007-12-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1846-54     Citation Subset:  IM    
Dept. of Neural and Behavioral Sciences H181, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
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MeSH Terms
Aging / physiology
Benzazepines / pharmacology
Body Weight / physiology
Conditioning, Operant / physiology*
Dopamine Antagonists / pharmacology*
Dose-Response Relationship, Drug
Food Preferences / physiology*
Glucose Tolerance Test
Prediabetic State / metabolism
Psychomotor Performance / physiology*
Raclopride / pharmacology
Rats, Inbred OLETF
Receptors, Dopamine D1 / antagonists & inhibitors
Receptors, Dopamine D2 / antagonists & inhibitors*
Reinforcement Schedule
Sucrose / pharmacology*
Grant Support
Reg. No./Substance:
0/Benzazepines; 0/Dopamine Antagonists; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 57-50-1/Sucrose; 84225-95-6/Raclopride

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