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

压力对恐惧学习、乙醇消耗和焦虑影响的异质性

基本信息

批准号：
9484109
负责人：
Michael S Fanselow
金额：
$ 37万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-12 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9484109
关键词：
AMPA Receptors Address Affect Alcohol abuse Alcohol consumption Amygdaloid structure Animal Model Animals Antisense Oligonucleotides Anxiety Behavior Behavioral Biological Biological Markers Biology Brain Comorbidity Data Data Set Development Discriminant Analysis Disease Event Extinction (Psychology)Fostering Freezing Fright Glucocorticoid Receptor Goals Heterogeneity Hippocampus (Brain)Human Impairment Individual Learning Life Logistic Regressions Measures Medial Modeling Phenotype Population Post-Traumatic Stress Disorders Predisposition Prefrontal Cortex Procedures Protein Subunits Proteins Publishing Rattus Refractory Reporting Research Rodent Series Shock Statistical Data Interpretation Stress Subgroup Suggestion Symptoms Syndrome Testing Time Trauma Up-Regulation Woman Work base conditioned fear consumption measures differential expression experience experimental study novel prevent receptor resilience stressor tool

项目摘要

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.

项目摘要在经历过创伤性、危及生命的事件的人中，有一小部分人会发展出一种称为创伤后应激障碍（PTSD）的病症，其特征是高度焦虑和恐惧处理受到干扰。这种情况在女性中更为普遍。此外，PTSD 是高度共病的与其他精神疾病，特别是酗酒有关。我们开发了一种动物模型来捕捉创伤后应激障碍（PTSD）的许多特征，因此应该有助于加深对生物机制的理解。导致疾病的变化并提出新的治疗方法。这里我们建议使用较温和的压力比我们在已发表的作品中使用的要多，因为它以较小的比例产生增强的恐惧学习动物（18%）的比例更接近人类的 PTSD 发生率。受到这种压力的老鼠会对焦虑、恐惧处理改变和酒精摄入量等多项指标进行测试。我们将用它作为工具来了解 PTSD 症状如何组合在一起形成亚型以及这些亚型与导致适应不良行为的大脑变化。