Sustaining factors for stress-induced emotional feeding in females

描述(由申请者提供)：长期暴露于心理社会应激源导致的情绪喂养可能是食物摄入量过高的关键因素。这对女性来说可能特别重要，她们一直报告说，压力导致的进食更多，肥胖率更高。普遍接受的观点是，高热量饮食的情绪喂养是一种形式 自我用药来缓解压力的行为和生理表现。虽然这件事 可能是这样，情绪喂养也可能是多巴胺(DA)奖励通路受损的结果，因为长期的心理社会应激通过减少中脑边缘区域的DA 2受体(D2R)而增加对成瘾表型的易感性，从而产生低多巴胺能状态。此外，简单地食用高热量饮食可以减少这些区域的D2R，但仅限于某些动物。因此，用高热量饮食自我用药可能会进一步损害应激诱导的DA系统功能低下。显然，对于未解决的压力，这不是一个健康的应对策略。对于试图节食的女性来说，一个特别重要的问题是，面对生活方式的变化，这些由压力引起的变化，包括DA功能受损，是否会持续下去。我们使用雌性恒河猴的社会从属关系作为女性慢性心理社会压力的模型的初步数据表明，情况可能是这样，因为在给予高卡路里饮食(HCD)时，从属雌性猕猴消耗的卡路里明显更多，当只有更健康的饮食可用时，这种过度吞噬现象持续存在。然而，尚不清楚的是，在这些健康的饮食条件下，这种模式是如何继续的。同样，目前尚不清楚，缓解慢性心理社会压力是否会恢复卡路里限制，或者即使在压力消除后，包括DA在内的食欲调节系统的变化是否会持续下去。利用社会寄养的雌性恒河猴作为女性的翻译模型，该项目将确定维持情绪喂养的机制。目标1将确定由社会从属引起的慢性社会压力是否维持HCD的过量摄入，以及暴露于急性应激源是否会加剧这种情况。目标2将检验这样一种假设，即摄入高热量饮食会降低中边缘区域DR2的可用性，而这将因社会从属关系而加剧。目标3将 测试假设，当有LCD时，雌二醇将更有效地抑制占主导地位的女性的卡路里摄入量，但当有HCD时，将促进卡路里摄入量，特别是在从属女性中。在目标4中，我们将使用两种干预策略来进一步阐明社会压力如何维持情绪喂养：1)尽管用更健康的低卡路里饮食取代了HCD，但下属的吞噬过度和D2R结合潜力降低将持续存在；以及2)通过改变社会地位来减少社会压力将改善但不是共同正常化D2R的供应或食物摄入量，这些研究将增加我们对维持情绪喂养的因素的理解，即使在健康的饮食环境中也是如此。

DESCRIPTION (provided by applicant): Emotional feeding resulting from chronic exposure to psychosocial stressors is likely a key factor for excess food intake. This may be particularly important for women, who consistently report more stress-induced eating and have higher rates of obesity. The well-accepted notion is that emotional feeding of calorically dense diets is a form of self-medication to relieve the behavioral and physiological manifestations of stress. While this may be the case, it is also probable that emotional feeding is the result of compromised dopamine (DA) reward pathways, as exposure to chronic psychosocial stress increases susceptibility to an addictive phenotype by reducing DA 2 receptors (D2R) in mesolimbic regions, producing a hypodopaminergic condition. Furthermore, simply eating a calorically dense diet reduces D2R in these regions but only in some animals. Thus, self-medicating with high caloric diets may further compromise the stress-induced hypofunctional DA system. Clearly, this is not a healthy coping strategy for unresolved stress. An issue particularly important for women attempting to diet is whether these stress-induced changes, including impaired DA function, persist in the face of life style changes. Our preliminary data using social subordination in female rhesus monkeys as a model of chronic psychosocial stress in women suggests this may be the case, as subordinate females consume significantly more calories when given a high caloric diet (HCD) and this hyperphagia persists when a healthier diet is exclusively available. What is not known, however, is how this pattern continues under these healthy dietary conditions. Similarly, it is unknown if the alleviation of chronic psychosocial stress will restore caloric restraint, or if changes in systems regulating appetite, including DA, persist even after stress is resolved. Using socially housed female rhesus monkeys as a translational model for women, this project will identify mechanisms that sustain emotional feeding. Aim 1 will determine whether chronic social stress induced by social subordination sustains excessive intake of a HCD and whether this is exacerbated by exposure to acute stressors. Aim 2 will test the hypothesis that intake of a calorically dense diet will reduce DR2 availability in mesolimbic regions and this will be exacerbated by social subordination. Aim 3 will test the hypothesis that estradiol will be more effective suppressing caloric intake in dominant females when a LCD is available but will promote caloric intake when an HCd is available, particularly in subordinate females. in a Aim 4 will use two intervention strategies to further elucidate how social stress sustains emotional feeding: 1) despite replacing a HCD with a healthier low caloric diet, hyperphagia and reduced D2R binding potential in subordinates will persist; and 2) reducing social stress by changing social status will improve but not normalize D2R availability or food intake Together, these studies will increase our understanding of factors that sustain emotional feeding, even in a healthy dietary environment.