Dopamine D2 receptors contribute to increased avidity for sucrose in obese rats lacking CCK-1 receptors.
Accumulating evidence has indicated a link between dopamine signaling and obesity in both animals and humans. We have recently demonstrated heightened avidity to sapid sweet solutions in the obese cholecystokinin (CCK)-1 receptor deficient Otsuka Long Evans Tokushima fatty (OLETF) rat. To investigate the dopamine dependence and the respective contribution of D1 and D2 receptor subtypes in this phenomenon, real and sham intake of 0.3 M sucrose solution was compared between prediabetic, obese OLETF and age-matched lean Long-Evans Tokushima Otsuka (LETO) cohorts following peripheral (i.p.) administration of equimolar doses (50-800 nmol/kg) of the D1 (R-(+) 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine, SCH23390) and D2 (raclopride) selective receptor antagonists. Both antagonists were potent in reducing sucrose intake in both strains with both drugs suppressing sham intake starting at lower doses than real intake (200 nmol/kg vs. 400 nmol/kg for SCH23390, and 400 nmol/kg vs. 600 nmol/kg for raclopride, respectively). Furthermore, when percent suppression of intake, a measure that controlled for the higher baseline sucrose intake by obese rats was analyzed, OLETF rats expressed an increased sensitivity to raclopride in reducing ingestion of sucrose with a 1.7- and 2.9-fold lower inhibitory dose threshold (ID50) for real and sham intake conditions, respectively, compared with LETO controls. In contrast, SCH23390 caused no differential strain effect with respect to dosage whether sucrose was real or sham fed. These findings demonstrate that D2 receptors are involved in heightened increased consumption of sucrose observed in the OLETF obese rat.
Hajnal
A
A
Department of Neural and Behavioral Sciences H181, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA. ahajnal@psu.edu
De Jonghe
B C
BC
Covasa
M
M
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D008297:Male; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF; D043886:Receptor, Cholecystokinin A / Q000172:deficiency / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013395:Sucrose / Q000008:administration & dosage*; D013549:Sweetening Agents / Q000008:administration & dosage*; D013649:Taste; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D043886:Receptor, Cholecystokinin A; D017448:Receptors, Dopamine D2; D013549:Sweetening Agents; D020891:Raclopride; D013395:Sucrose