Obesogenic diets may differentially alter dopamine control of sucrose and fructose intake in rats

Chronic overeating of obesogenic diets can lead to obesity, reduced dopamine signaling, and increased consumption of added sugars to compensate for blunted reward. However, the specific role of diet composition yet remains unknown. To study this, Sprague–Dawley male rats were fed a high-energy diet with high fat and low carbohydrate content (HFHE), a fat-sugar combination high-energy diet (FCHE), or standard chow for 24 weeks. We found that both high-energy diets produced substantial body weight gain compared to chow-fed controls. To investigate dopamine control of short (2-h) intake of palatable sucrose or fructose solutions, rats were pretreated peripherally (IP) with equimolar doses (0–600 nmol/kg) of the dopamine D1 (SCH23390) and D2 (raclopride) subtype-specific receptor antagonists. The results showed an overall increase in the efficacy of D1 and D2 receptor antagonists on suppression of intake in obese rats compared to lean rats, with effects differing based on diets and test solutions. Specifically, SCH23390 potently reduced both sucrose and fructose intake in all groups; however, lower doses were more effective in HFHE rats. In contrast, raclopride was most effective at reducing fructose intake in the obese FCHE rats. Thus, it appears that obesity due to the consumption of combinations of dietary fat and sugar rather than extra calories from dietary fat alone may result in reduced D2 receptor signaling. Furthermore, such deficits seem to preferentially affect the control of fructose intake. These findings demonstrate for the first time a plausible interaction between diet composition and dopamine control of carbohydrate intake in diet-induced obese rats. It also provides additional evidence that sucrose and fructose intake is regulated differentially by the dopamine system.

► High-energy diets independent of macronutrient content are potent to cause obesity.
► Diet composition appears to differentially alter dopamine receptor sensitivity.
► D1 receptor blockade reduced sucrose and fructose intake in lean and obese rats.
► D2 receptor blockade reduced sucrose intake in high fat fed, but not lean rats.
► D2 receptor blockade reduced fructose intake in fat-sugar fed rats only.