Behavioral and neural alterations of the ventral tegmental area by Cafeteria diet exposure in rats

The brain reward system is essential for regulating appetitive and consummatory behaviors in response to various incentive stimuli. Junk food, known for its high palatability, is particularly associated with the potential for excessive consumption. While previous studies have shown that excessive junk food intake can impact reward circuitry, the precise mechanisms remain unclear. Additionally, it is unknown whether the functionality of this brain system is similarly altered in response to other natural rewards. In this study, we used fiber photometry combined with a behavioral reward test to investigate how six weeks of excessive cafeteria (CAF) diet consumption affects VTA neural activity and behavioral responses to food and sexual rewards in sexually experienced female rats. For the first time, we demonstrate that prolonged exposure to a CAF diet decreases interest in a food reward, resulting in reduced consumption. These behavioral changes were accompanied by diminished neural activity in the VTA. Similarly, but to a lesser extent, reductions in VTA activity responses were observed in response to a sexual partner, although no significant behavioral differences were detected during sexual interactions. Furthermore, a two-week reversal diet of standard chow was insufficient to restore VTA neural activity in CAF-exposed animals, which continued to show decreased VTA responses to both food rewards and sexual partners. Our findings suggest that prolonged junk food exposure leads to desensitization of the VTA, a key node in the brain’s reward circuitry, resulting in reduced responsiveness to natural rewards.