Acute vs Chronic Stress-Enhanced Fear Learning

急性与慢性压力增强的恐惧学习

• 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
• 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

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， 创伤后应激障碍和重度抑郁症鉴于这些疾病的高发病率 如果我们想解决这些问题，了解基本的生物和心理过程是至关重要的。 严重的问题，并制定有效的治疗方法。文献中的一个问题是， （急性）暴露于压力或反复（慢性）压力具有类似的影响。第二个问题是， 必须强调是为了产生有害的影响。重复的轻度压力经历是否会增加 与更严重的急性应激源的影响相当吗慢性压力暴露是否有更大的影响 比同样强烈的急性压力体验更重要吗令人惊讶的是，虽然有大量的基础科学文献， 在压力下，这些文献根本无法回答这些问题。这是因为所采用的方法 完全混淆了压力的慢性性质和严重性。通常比较的是一系列 重复的压力源到同一压力的单一实例。但重复的例子意味着压力不是 只是慢性的，总体上也更严重。我们发明了一种方法 操纵压力的长期性和严重性，这将首次让我们准确地回答这些问题。 重要的问题这项工作开始于我们广泛使用一种强烈的急性应激源和数据库 对生理和行为的影响。急性应激源的设计让我们 把它分成15个“比特”，每天一比特，连续15天，因为急性应激会重复， 在90分钟内重复15次相同的厌恶刺激。我们也可以系统地改变厌恶刺激的强度， 体验.我们的初步数据已经表明，慢性和急性压力引起不同的行为， 应答我们的第一个目标是检验这样一个假设，即这些差异的发生是因为急性压力进入了一组 当慢性压力进入学习或联想条件反射时， 流程.我们的第二个目标集中在生理和神经的变化，是不同的激发 由慢性和急性压力源引起的。此外，我们将确定压力的严重程度，而不是慢性程度 是罪魁祸首第三个目标集中在旨在阻止压力影响的操作，以帮助阐明 压力的长期性和严重性如何通过不同的生物学机制产生影响。我们也 假设男性和女性对压力源的严重程度有不同的阈值， 行为上不适应的变化。如果这一假设成立，开始可以帮助解释为什么焦虑症和 抑郁症在女性中更为普遍。

项目成果

PAC1 receptor modulation of freezing and flight behavior in periaqueductal gray.

• DOI: 10.1111/gbb.12873
• 发表时间: 2023-12
• 期刊: Genes, brain, and behavior

Negative valence systems: sustained threat and the predatory imminence continuum.

• DOI: 10.1042/etls20220003
• 发表时间: 2022-12-09
• 期刊: Emerging topics in life sciences
• 影响因子: 3.8

Dissociable consequences of moderate and high volume stress are mediated by the differential energetic demands of stress.

• DOI: 10.1371/journal.pone.0273803
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7