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Background Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb. Methods First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-Acb NPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb. Results In rats on the free-choice, high-fat, high-sugar diet, intra-Acb NPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-Acb NPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acb enkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb. Conclusions NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-Acb NPY-induced fat intake.

High-energy diets that induce obesity decrease striatal dopamine D 2/3 receptor (DRD 2/3 ) availability. It is however poorly understood which components of these diets are underlying this decrease. This study assessed the role of saturated fat intake on striatal DRD 2/3 availability. Forty rats were randomized to a free-choice high-fat high-sugar diet (HFHS) or a standard chow diet for 28 days. Striatal DRD 2/3 availability was measured using 123 I-IBZM storage phosphor imaging at day 29. The HFHS group was split in a HFHS-high-fat (HFHS-hf) and HFHS-low-fat (HFHS-lf) group based on the percentage energy intake from fat. Rats of both HFHS subgroups had increased energy intake, abdominal fat stores and plasma leptin levels compared with controls. DRD 2/3 availability in the nucleus accumbens (NAcc) was significantly lower in HFHS-hf than in HFHS-lf rats, whereas it was similar for HFHS-lf and control rats. Furthermore, DRD 2/3 availability in the NAcc was positively correlated with the percentage energy intake from sugar. Total energy intake was lower for HFHS-hf than for HFHS-lf rats. Together these results suggest that a diet with a high fat/carbohydrate ratio, but not total energy intake or the level of adiposity, is the best explanation for the decrease in striatal DRD 2/3 availability observed in diet-induced obesity.International Journal of Obesity (2013) 37, 754-757; doi:10.1038/ijo.2012.128; published online 7 August 2012Keywords: free-choice high-fat high-sugar diet; diet-induced obesity; dopamine D 2/3 receptor; striatum; energy intake; saturated fat INTRODUCTION High-fat (HF) and cafeteria diets induce obesity in rodents and decrease striatal dopamine D 2/3 receptor (DRD 2/3 ) levels [1][2][3] Imaging studies in humans also demonstrate that striatal DRD 2/3 availability is lower in obese subjects. 4,5 However, the mechanisms of action underlying this decrease remain poorly understood. Midbrain leptin receptors may have a role, as they mediate the decrease in extracellular dopamine levels in the nucleus accumbens (NAcc) by a HF diet. 6 In addition, knockdown of the dopamine D 2 receptor in the striatum is associated with increased reward deficiency and compulsive eating behavior in rats.1 This can be related to the alternative hypothesis that low DRD 2/3 levels might be a downregulation due to overstimulation of the dopamine system by repetitive food intake in obesity. 4 It remains unclear though whether increased total energy intake by high-energy diets or specific dietary components (for example, saturated fat, carbohydrates) underlie the induction of lower striatal DRD 2/3 levels.We previously showed that rats on a choice diet with saturated fat and a sugar solution (high-fat high-sugar, HFHS) become hyperphagic and obese. 7 We observed that some rats prefer saturated fat whereas others prefer the sugar solution although they all become obese. This variety allows us to determine whether diet composition or total energy intake is involved in DRD 2/3 downregulation. As we recently demonstrated that ra...