TY - JOUR
T1 - Altered dopamine D2 receptor function and binding in obese OLETF rat
AU - Hajnal, Andras
AU - Margas, Wojciech M.
AU - Covasa, Mihai
N1 - Funding Information:
The authors wish to thank Otsuka Pharmaceutical Co. (Tokushima, Japan) for the generous donation of the OLETF and LETO animals used to perform this research and Drs. Bello and Khokhar for their assistance with the receptor binding assays. This research was supported by National Institute of Diabetes & Digestive & Kidney Diseases Grant DK065709.
PY - 2008/1/31
Y1 - 2008/1/31
N2 - A decrease in D2-like receptor (D2R) binding in the striatum has been reported in obese individuals and drug addicts. Although natural and drug rewards share neural substrates, it is not clear whether such effects also contribute to overeating on palatable meals as an antecedent of dietary obesity. Therefore, we investigated receptor density and the effect of the D2R agonist quinpirole (0.05, 0.5 mg/kg, S.C.) on locomotor activity and sucrose intake in a rat model of diet-induced obesity, the CCK-1 receptor-deficient Otsuka Long Evans Tokushima Fatty (OLETF) rat. Compared to age-matched lean controls (LETO), OLETF rats expressed significantly lower [125I]-iodosulpride binding in the accumbens shell (-16%, p < 0.02). Whereas the high dose of quinpirole increased motor activity in both strains equally, the low dose reduced activity more in OLETF. Both doses significantly reduced sucrose intake in OLETF but not LETO rats. These findings demonstrate an altered D2R signaling in obese OLETF rats similar to drug-induced sensitization and suggest a link between this effect and avidity for sucrose in this model.
AB - A decrease in D2-like receptor (D2R) binding in the striatum has been reported in obese individuals and drug addicts. Although natural and drug rewards share neural substrates, it is not clear whether such effects also contribute to overeating on palatable meals as an antecedent of dietary obesity. Therefore, we investigated receptor density and the effect of the D2R agonist quinpirole (0.05, 0.5 mg/kg, S.C.) on locomotor activity and sucrose intake in a rat model of diet-induced obesity, the CCK-1 receptor-deficient Otsuka Long Evans Tokushima Fatty (OLETF) rat. Compared to age-matched lean controls (LETO), OLETF rats expressed significantly lower [125I]-iodosulpride binding in the accumbens shell (-16%, p < 0.02). Whereas the high dose of quinpirole increased motor activity in both strains equally, the low dose reduced activity more in OLETF. Both doses significantly reduced sucrose intake in OLETF but not LETO rats. These findings demonstrate an altered D2R signaling in obese OLETF rats similar to drug-induced sensitization and suggest a link between this effect and avidity for sucrose in this model.
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U2 - 10.1016/j.brainresbull.2007.07.019
DO - 10.1016/j.brainresbull.2007.07.019
M3 - Article
C2 - 18158098
AN - SCOPUS:37249094197
SN - 0361-9230
VL - 75
SP - 70
EP - 76
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 1
ER -