Heterogeneity in Stress Effects on Fear Learning, Ethanol Consumption and Anxiety

项目摘要 在经历过创伤性、危及生命的事件的人中，有一小部分人会患上 一种称为创伤后应激障碍(PTSD)的疾病，其特征是高度焦虑和 惊慌失措的恐惧处理。这种情况在女性中更为普遍。此外，创伤后应激障碍高度并存 有其他精神疾病，特别是酗酒。我们已经开发出一种动物模型，可以捕捉到 创伤后应激障碍的许多特征和因此应该有助于发展对生物学的理解 导致这种疾病的变化，并提出了新的治疗方法。在这里，我们建议使用较温和的重音 比我们在已发表的研究中使用的更多，因为它以更小的比例产生增强的恐惧学习 动物(18%)更接近于人类的创伤后应激障碍的发生率。受到这种压力的大鼠会 在焦虑、恐惧处理和酒精摄入量的多项指标上进行测试。我们将以此作为 该工具用于了解创伤后应激障碍症状如何分组形成亚型，以及这些亚型与 导致不适应行为的大脑变化。

PROJECT ABSTRACT A small but significant percentage of people that experience a traumatic, life-threatening, event develop a condition called Post-Traumatic Stress Disorder (PTSD), which is characterized by heightened anxiety and disturbed fear processing. The condition is more prevalent in women. Additionally, PTSD is highly comorbid with other psychiatric conditions notably alcohol abuse. We have developed an animal model that captures many of the features of PTSD and as such should be helpful in developing an understanding of the biological changes that produce the disorder and suggesting novel treatments. Here we propose to use a milder stress than we have used in our published work because it produces enhanced fear learning in a smaller proportion of animals (18%) that better approximates the rate of PTSD in humans. The rats subjected to this stress will be tested on a number of measures of anxiety, altered fear processing and alcohol intake. We will use this as a tool to understand how PTSD symptoms group together to form subtypes and how these subtypes relate to the brain changes that cause maladaptive behavior.