Background: Obesity is a modern health epidemic, with the overconsumption of highly palatable, calorically dense foods as a likely contributor. Despite the known consequences of obesity, behavioral noncompliance remains high, supporting the powerful rewarding properties of such foods. We hypothesized that exposure to preferred diets would result in an amelioration of stress responsivity via activation of reward pathways that would be reversed during dietary withdrawal, increasing the risk for relapse and treatment failure.
Methods: Mice were exposed to preferred diets high in fat or carbohydrates for 4 weeks and then were withdrawn to house chow. Behavioral, physiologic, and biochemical assays were performed to examine changes in stress and reward pathways.
Results: These studies revealed significant changes in arousal and anxiety-like behaviors, limbic corticotropin-releasing factor expression, and expression of reward-related signaling molecules in response to the highly preferred high-fat diet that was reversed by withdrawal. In a dietary-reinstatement model, mice withdrawn from the high-fat diet endured an aversive environment to gain access to the preferred food.
Conclusions: Exposure to a highly preferred diet high in fat reduces stress sensitivity, whereas acute withdrawal from such a diet elevates the stress state and reduces reward, contributing to the drive for dietary relapse.