Saturated and unsaturated high-fat diets induce addictive-like behavior in an animal model of operant self-administration

In recent years, obesity has become a significant public health concern worldwide. The rapid increase in prevalence is often attributed to the overconsumption of highly palatable, calorically dense foods that are rich in sugars and fats. These dietary habits have been shown to modulate specific brain circuits, notably the mesolimbic dopaminergic reward system. Despite extensive research into their effects, the potential reinforcing properties of these diets are still unknown. We conducted a study using two high-fat diets devoid of added sugar (SOLF, which is high in saturated fats and UOLF, high in unsaturated fats). We utilized an operant self-administration model with Skinner boxes, following a three-criteria protocol: 1) reward-seeking behavior, 2) motivation to obtain the reward, and 3) compulsivity. Juvenile C57BL/6J mice, both male and female, were subjected to an incremental reinforcement schedule followed by a progressive ratio session aimed at finding the breaking point, and finally, two cue-induced reinstatement sessions following the extinction of the food seeking behavior. Our results show that both diets induce potent seeking behavior for the high-fat food, characterized by high levels of compulsivity and great motivation to obtain the reward. These findings suggest that sugar-free high-fat diets function as potent reinforcers, capable of inducing addictive-like behaviors. Notably, differences between SOLF and UOLF are primarily observed in the breaking point and following the extinction of the seeking behavior, with higher values observed for UOLF.