The involvement of the dopamine-3 receptor in the regulation and reward of food intake

The DA receptors (DA-R) have been identified as potential targets for understanding processing of reward related behavior. The dopamine-3 receptor (D3-R) is expressed in the midbrain dopaminergic circuitry suggesting DA signaling at the D3-R may be vital to inhibition of reward processing. Mice lacking the D3-R (D3-R −/−) and wild-types (D3-R +/+) were given 3-month access to standard rodent chow or a preferable, high-fat (HF) diet. Following 3-months of access, mice were sacrificed and body weight, adiposity, food intake, plasma insulin and leptin, and metabolic measures were evaluated. D3-R −/− became obese on the preferable, HF diet but lacked an overt food intake phenotype. Thus, it was hypothesized that signaling at the D3-R enables an animal to integrate signals about peripheral energy availability and adjust food intake appropriately. Mercaptoacetate (MA), 2-deoxy-d-glucose (2-DG) and insulin were ineffective at increasing food intake in D3-R −/− mice, however peripheral glucose and fatty acids were elevated normally in response to the drugs. In contrast, the mutant mice were hyper-responsive to the anorectic effects of leptin and amylin. To further characterize reward-related behavior the D3-R −/− and +/+ mice were given access to increasing concentrations of ethanol. Ethanol intake is of interest because dopaminergic circuitry has been hypothesized to mediate consumption and is a caloric source with psycho-pharmacological properties. There was a genotypic based increased consumption by the D3-R −/− mice. To assess the hypothesized inhibitory role of the D3-R on food intake we administered the D3-R agonist (7-OH-DPAT) to rats with access to chow or HF diet in three different feeding regimens of varying levels of deprivation. In a final group of experiments animals with access to chow or HF diet were food restricted. On the test day 7-OH-DPAT was administered to animals that received the diet that was expected or the diet that violated expectancy (positive and negative expectancy). 7-OH-DPAT reduced intake of the positive contrast without reducing intake in the other conditions. To characterize central populations of D3-Rs that may influence this effect 7-OH-DPAT was administered directly into the nucleus accumbens (NAcc) or the lateral hypothalamus (LH) in the same behavioral paradigm.