Obesity has reached alarming rates across the planet. While excessive caloric intake constitutes the leading cause of this epidemic, the identities of the neurobiological mechanisms underlying overeating remain unclear. Sugar consumption levels remain well beyond recommended daily intake levels, with sugar-sweetened beverages being the largest source of added calories in our diets. Epidemiological studies report strong associations between sugar-sweetened beverage intake and weight gain, obesity and related long-term metabolic diseases. From a behavioral standpoint, sustained consumption of sugar-sweetened beverages despite deleterious consequences constitutes a type of inflexible behavior. It has been shown that dopamine release in dorsal striatum is critical for the formation of inflexible behaviors, and that sugar intake produces significantly greater levels of dopamine efflux when compared to artificial sweeteners in dorsal striatum. In the present study we aimed at characterizing the effectors acting downstream of dopamine release to generate inflexible behaviors. Specifically, we tested the hypothesis that repeated exposure to caloric, but not to non-caloric, sweeteners induce inflexible intake by activating striato-nigral pathways. Accordingly, we developed in rodents a sugar-induced inflexible behavior model, and employed a combination of neurochemical, molecular and optogenetic methods to unveil the pathways downstream to dopamine release that control behavioral inflexibility associated to sugar intake. Our results show that i) Chronic sugar exposure strongly predisposes animals to behavioral inflexibility by rendering them less sensitive to reward devaluation; ii) Optogenetic and cell-specific ablation studies show that striato-nigral pathways are necessary and sufficient for the expression of inflexible sugar intake; and iii) Optical activation of nigral circuits increases sensitivity to reward devaluation by opposing the stimulatory influence of striatal neurons. Our data reveals a new neural pathway via which repeated glucose exposure leads to less sensitivity to the deleterious aspects of high-sugar intake.