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.