? The literature clearly demonstrates that food intake and energy balance are profoundly influenced by stress, and vice versa. However, the neural mechanisms underlying these effects are largely unknown. My career goal is to establish an independent academic research program focused on pursuing the mechanisms by which stress and food/energy balance interact. To begin addressing these interactions, I have developed a model of limited palatable food intake in which rats with free access to food and water are given additional twice daily access to a small amount of sucrose versus water. In this model, sucrose rats show attenuated hypothalamic-pituitary-adrenal (HPA) axis responses to stress and diminished stress-induced neuronal activation in brain reward regions. Moreover, the calories and other post-ingestive consequences of sucrose are neither sufficient nor necessary for the HPA dampening. I hypothesize that activation of brain reward pathways by the highly-palatable sucrose mediates the reduced stress responsiveness. The present proposal tests this hypothesis by using (1) molecular approaches to determine whether a history of limited sucrose intake alters brain reward pathways similar to other types of reward, (2) pharmacological activation of brain reward pathways to determine whether their activation is sufficient for HPA dampening, and (3) excitotoxic lesions of principal brain reward regions to determine whether activity in these regions is necessary for sucrose-mediated HPA dampening. Success in this area of inquiry necessitates a solid background in stress, energy balance, and reward research. My background in stress regulation is strong, and additional expertise in the areas of energy balance and reward, as provided by the proposed research project, coursework, training environment, and career development activities, would greatly enhance my ability to obtain independent funding and pursue an independent research career at the juncture of these highly-interconnected fields. Lastly, the proposed work has important implications for public health. When under stress, many people increase their intake of highly palatable (e.g. tasty high-sugar or high-fat) foods, presumably to help calm or comfort themselves. However, this behavior can increase body weight and contribute to the development of obesity. This project seeks to understand how palatable foods act to decrease the response to stress, thereby providing insight into the motivation to consume these foods and potentially offering new strategies for the prevention and treatment of obesity. ? ? ?
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