Involvement of the dorsomedial prefrontal cortex in high-fat food conditioning in adolescent mice

•High-fat diets (HFD) activate the prefrontal cortex (PFC) in adolescent mice.•HFD trigger robust conditioned place-preference (CPP) behavior.•HFD evoke food-seeking behavior.•Intensity of HFD-evoked CPP positively correlates with D1r expression in the PFC.•Expression of Per2 in the PFC is lower in mice with strong CPP.

Our hypothesis is that direct targeting of brain areas involved in the perception of food as a rewarding stimulus accounts for initial hyperphagia caused by high-fat food (HFD). Because adolescents are more sensitive than adults to HFD, studies were performed in five-week old male mice. We analyzed the effect of acute exposition to HFD on c-Fos immunolabeling and we observed that this diet selectively increased c-Fos immunolabeling in the dorsomedial prefrontal cortex (PFC). Furthermore HFD triggered strong and long-lasting conditioned place-preference (CPP) behavior. We also found that the strength of conditioning correlated with the up-regulation of the expression of genes involved in dopaminergic transmission together with a decreased expression of the Per2 gene in the CPF. Our data are coherent with the involvement of the dorsomedial PFC in the perception of HFD as a positive reinforcer and suggest that sensory stimuli activate this brain area after HFD intake.