Social stress-induced changes in energy homeostasis

描述（由申请人提供）：暴露于压力会引起动物和人类的行为和生理反应，包括食物摄入量和体重的变化。这个提议将利用一种独特的动物社会压力模型——可见洞穴系统（VBS）。VBS提供了一种半自然的环境，在这种环境中，雄性大鼠之间自然地形成了支配等级，产生了支配（DOM）和从属（SUB）动物，这些动物可以很容易地通过最小的实验者干预来识别。虽然已经可靠地观察到亚组患者体重的显著变化，但对其病因知之甚少。此外，慢性社会压力导致的体重调节改变的长期后果尚未在该模型中得到检验。拟议的实验将为理解这些和其他人类压力相关的条件奠定基础，并可能指出新的治疗策略。具体目的是：1)验证在VBS居住期间下属体重减轻是由于食物摄入减少和/或能量消耗增加的假设；2)验证在VBS中慢性应激14天后明显的生理、内分泌和神经化学变化在允许动物在VBS外恢复后将恢复到控制水平的假设。第二种假设是，在恢复过程中，SUB会优先以脂肪组织的形式增加体重，而DOM会主要以瘦体重的形式增加体重。3)为了验证多次、间歇性的社会压力发作会比一次发作产生更严重、更持久的脑神经化学和能量稳态变化的假设。

DESCRIPTION (provided by applicant): Exposure to stress elicits behavioral and physiological responses in animals and humans, including changes in food intake and body weight. This proposal will take advantage of a unique animal model of social stress, the Visible Burrow System (VBS). The VBS provides a semi-naturalistic environment in which a dominance hierarchy naturally develops among male rats producing dominant (DOM) and subordinate (SUB) animals that can be easily identified with minimal experimenter intervention. Although significant changes in body weight among the SUB group have been reliably observed, little if anything is known of its etiology. In addition, the long-term consequences of altered body weight regulation resulting from chronic social stress have not been examined in this model. The proposed experiments will lay the groundwork for understanding these and other stress-related conditions in humans and may point to novel therapeutic strategies. The specific aims are: 1) to test the hypothesis that body weight loss in subordinates during VBS housing is attributable to decreased food intake and/or to increases in energy expenditure, 2) to test the hypothesis that physiological, endocrine and neurochemical changes that are evident following 14 days of chronic stress in the VBS will return to control levels when the animals are allowed to recover outside the VBS. A secondary hypothesis is that SUB will gain weight during recovery preferentially as adipose tissue and DOM will gain weight primarily as lean body mass, 3) to test the hypothesis that multiple, intermittent episodes of social stress produce more severe and enduring changes of brain neurochemistry and energy homeostasis than a single episode.