Acute vs Chronic Stress-Enhanced Fear Learning

急性与慢性压力增强的恐惧学习

基本信息

批准号：
10368978
负责人：
Michael S Fanselow
金额：
$ 37.94万
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：
2018
资助国家：
美国
起止时间：
2018-05-17 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10368978
关键词：
Acute Address Amygdaloid structure Anxiety Anxiety Disorders Aversive Stimulus Basic Science Behavior Behavioral Biological Brain Chronic Chronic stress Circadian Rhythms Clinical Corticosterone Cues Data Data Set Databases Disease Diurnal Rhythm Exposure to Extinction (Psychology)Female Fright Future Glucocorticoid Receptor Goals Health behavior High Prevalence Hippocampus (Brain)Learning Literature Major Depressive Disorder Mediating Memory Mental Depression Methodology Methods N-Methyl-D-Aspartate Receptors Nature Pathology Phenotype Physiological Physiology Post-Traumatic Stress Disorders Prefrontal Cortex Preparation Probability Process Proteins Publishing Rattus Recurrence Research Series Severities Shapes Shock Signal Transduction Stimulus Stress Stressful Event Testing Time Translating Work acute stress anxiety-like behavior behavior influence behavioral response classical conditioning conditioned fear design effective therapy experience fear memory ghrelin hypothalamic-pituitary-adrenal axis indexing interest male neuromechanism novel pre-clinical psychologic relating to nervous system response restraint sex stressor virtual

项目摘要

Project Abstract Stress can have a profound detrimental impact on our behavior, predisposing us to anxiety disorders such as post-traumatic stress disorder and major depression. Given the high prevalence of these disorders understanding the basic biological and psychological processes is vitally important if we wish to address these significant problems and develop effective treatments. One question in the literature is whether a single (acute) exposure to stress or repeated (chronic) stress has similar effects. A second question is how severe must stress be in order to produce detrimental effects. Do repeated mild stressful experiences have an added impact that equals that of a more severe acute stressor? Does chronic stress exposure have a greater impact than an equally intense acute stressful experience? Surprisingly, while there is a large basic science literature on stress, that literature simply does not answer these questions. This is because the methods employed have totally confounded the chronic nature of stress with its severity. Typically what is compared are a series of repeated stressors to a single instance of the same stress. But repeated instances mean that the stress is not only chronic it is also, in total, more severe. We have developed a method were we can independently manipulate the chronicity and severity of stress that will for the first time allow us to accurately answer these important questions. The work begins from our extensive use of an intense acute stressor and the database we have collected on its effects on physiology and behavior. The design of our acute stressor allows us to break it into 15 “bits” than can be administered at one bit a day for 15 days because the acute stress repeats the same aversive stimulus 15 times over 90 min. We can also systematically vary the intensity of our aversive experience. Our preliminary data already indicate that chronic and acute stress provokes different behavioral responses. Our first aim tests the hypothesis that the differences occur because acute stress taps into a set of automatic “nonassociative” processes while chronic stress taps into learning or associative conditioning processes. Our second aim focuses on the physiological and neural changes that are differentially provoked by chronic vs acute stressors. Additionally, we will determine to what extent stress severity and not chronicity is the culprit. The third aim focuses on manipulations designed to block the effects of stress to help elucidate how stress chronicity and severity produce their effects via different biological mechanisms. We also hypothesize that males and females have different thresholds for how severe a stressor must be to provoke maladaptive changes in behavior. That hypothesis if true can begin to help explain why anxiety disorders and depression are more prevalent in females.

项目摘要压力会对我们的行为产生深远的有害影响，使我们容易患上焦虑症，例如鉴于这些疾病的患病率很高，创伤后应激障碍和重度抑郁症。如果我们希望解决这些问题，了解基本的生物和心理过程至关重要文献中的一个问题是是否存在单一的方法来解决重大问题并制定有效的治疗方法。（急性）压力或反复（慢性）压力具有类似的影响第二个问题是有多严重。重复的轻微压力经历是否会产生不良影响？与更严重的急性压力源的影响相同吗？慢性压力暴露的影响更大吗？令人惊讶的是，尽管有大量的基础科学文献，就压力而言，文献根本无法回答这些问题，这是因为所采用的方法已经存在。完全混淆了压力的长期性质及其严重程度。通常比较的是一系列的压力。相同压力的单个实例出现重复的压力源，但重复的实例意味着压力不是压力。只是慢性的，总的来说，它也更严重，我们已经开发出一种我们可以独立进行的方法。控制压力的长期性和严重性，这将让我们第一次能够准确地回答这些问题这项工作始于我们对强烈急性压力源和数据库的广泛使用。我们收集了它对生理和行为的影响。急性压力源的设计使我们能够将其分成 15 个“小块”，这样可以每天服用一小块，持续 15 天，因为急性应激会重复出现在 90 分钟内重复相同的厌恶刺激 15 次，我们还可以系统地改变厌恶的强度。我们的初步数据已经表明，慢性和急性压力会引发不同的行为。我们的第一个目标是检验这样一个假设：这种差异的发生是因为急性压力会影响到一系列反应。自动的“非联想”过程，而慢性压力会影响学习或联想调节我们的第二个目标侧重于不同引起的生理和神经变化。此外，我们将确定压力的严重程度而不是慢性程度。第三个目标是旨在阻止压力影响的操作，以帮助阐明。我们还了解压力的长期性和严重性如何通过不同的生物机制产生影响。研究发现，男性和女性对于激怒压力源的严重程度有不同的阈值如果这一假设成立，则可以开始帮助解释为什么焦虑症和行为发生适应不良的变化。抑郁症在女性中更为普遍。