Palatable Food, Reward, and Stress

描述(由申请人提供)： 文献清楚地表明，食物摄入量和能量平衡受到压力的深刻影响，反之亦然。然而，这些效应背后的神经机制在很大程度上是未知的。我的职业目标是建立一个独立的学术研究项目，专注于探索压力和食物/能量平衡相互作用的机制。为了开始解决这些相互作用，我开发了一个有限可口食物摄入量的模型，在这个模型中，自由获取食物和水的大鼠每天额外获得两次蔗糖而不是水。在这个模型中，蔗糖大鼠表现出下丘脑-垂体-肾上腺(HPA)轴对应激的反应减弱，并减少了应激诱导的脑奖赏区域神经元的激活。此外，蔗糖的卡路里和其他摄入后的后果既不足以抑制HPA，也不是必要的。我假设，高度可口的蔗糖激活了大脑奖励通路，介导了压力反应性的降低。目前的建议通过使用(1)分子方法来验证这一假说，以确定限制蔗糖摄入量的历史是否改变了类似于其他类型的奖励的大脑奖励途径，(2)大脑奖励途径的药理学激活以确定它们的激活是否足以抑制HPA，以及(3)主要大脑奖励区域的兴奋毒性损伤以确定这些区域的活动是否对于蔗糖介导的HPA抑制是必要的。在这个研究领域的成功需要在压力、能量平衡和奖励研究方面有扎实的背景。我在压力调节方面的背景很好，拟议的研究项目、课程、培训环境和职业发展活动提供了能量平衡和奖励领域的额外专业知识，将极大地提高我在这些高度关联的领域的交界点获得独立资金和追求独立研究事业的能力。最后，拟议的工作对公共卫生具有重要影响。当面临压力时，许多人会增加他们对美味(如可口的高糖或高脂肪)食物的摄入量，大概是为了帮助自己平静或安慰自己。然而，这种行为会增加体重，并有助于肥胖的发展。该项目旨在了解美味食物如何降低对压力的反应，从而提供对消费这些食物的动机的洞察，并有可能为预防和治疗肥胖症提供新的策略。

DESCRIPTION (provided by applicant): 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.