Altered dopamine D2 receptor function and binding in obese OLETF rat.
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.
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test / Q000379:methods; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D011485:Protein Binding / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D018491:Dopamine Agonists; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; C045105:iodosulpride; D019257:Quinpirole; D013395:Sucrose; D013469:Sulpiride