Social stress-induced changes in energy homeostasis

描述（由申请方提供）：暴露于压力会引起动物和人类的行为和生理反应，包括摄食量和体重的变化。这项建议将利用一种独特的社会压力动物模型，可见洞穴系统（VBS）。VBS提供了一个半自然主义的环境，在这种环境中，雄性大鼠产生的显性（DOM）和从属（DOM）动物之间自然地形成了一个显性层次结构，这些动物可以很容易地用最少的实验者干预来识别。虽然已经可靠地观察到了糖尿病组的体重显著变化，但对其病因知之甚少。此外，在这个模型中还没有研究长期的社会压力导致的体重调节改变的长期后果。拟议中的实验将为理解人类的这些和其他与压力相关的条件奠定基础，并可能指向新的治疗策略。具体目标是：1）检验在VBS圈养期间下属的体重减轻归因于食物摄入减少和/或能量消耗增加的假设，2）检验在VBS中慢性应激14天后明显的生理、内分泌和神经化学变化将在允许动物在VBS外恢复时恢复到对照水平的假设。第二个假设是，在恢复过程中，Dom将优先作为脂肪组织增加体重，而DOM将主要作为瘦体重增加体重，3）以检验以下假设：与单次事件相比，多次间歇性的社会压力事件会产生更严重和持久的脑神经化学和能量稳态变化。

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.