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

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