Stressor controllability and anxiety: role of serotonin and prefrontal cortex.

压力源可控性和焦虑：血清素和前额叶皮层的作用。

• 批准号: 7538872
• 负责人: John Paul Christianson
• 金额: $ 4.96万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538872
• 关键词: 8-Hydroxy-2-(di-n-propylamino)tetralin; Abbreviations; Adolescent; Adult; Affect; American; Amygdaloid structure; Anatomy; Anxiety; Area; Arousal; Aversive Stimulus; Basic Behavioral Science; Beds; Behavior; Behavior Control; Behavioral; Biological; Brain; CRH gene; Cell Nucleus; Chemosensitization; Cognitive; Complex; Condition; Conflict (Psychology); Control Locus; Corticotropin-Releasing Hormone; Development; Diagnosis; Event; Exposure to; Fright; Functional disorder; Goals; Home environment; Human; Hurricane; Immunohistochemistry; Individual; Injury; Knowledge; Laboratories; Left; Literature; Measures; Medial; Mediating; Mediator of activation protein; Methods; Microdialysis; Microinjections; Military Personnel; Muscimol; National Institute of Mental Health; Neurosciences; Numbers; Patients; Perception; Persian Gulf; Physiological; Physiological Adaptation; Picrotoxin; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevention; Procedures; Process; Psychological Impact; Publications; Rattus; Research; Research Design; Research Personnel; Research Priority; Research Training; Role; Selective Serotonin Reuptake Inhibitor; Series; Serotonin; Shock; Social Behavior; Social Interaction; Stimulus; Stress; Stress and Coping; Structure; System; Terrorism; Testing; Vietnam; Violence; Woman; classical conditioning; conditioned fear; coping; day; dorsal raphe nucleus; emotional stimulus; expectation; experience; gamma-Aminobutyric Acid; in vivo; insight; men; neural circuit; neuromechanism; physical abuse; prevent; programs; psychologic; relating to nervous system; research study; response; social; statistics; stressor

DESCRIPTION (provided by applicant): Prior research and human literature indicate that coping or the perception of control often mitigates the consequences of stressful experiences, but lack or control during stress may result in pathological responses. In the rat, much is known about the basic neural mechanisms that mediate the effects of controllable and uncontrollable stressors. Importantly, uncontrollable stressors cause activation of the serotonergic dorsal raphe nucleus while controllable stressors prevent this activation via inhibitory modulation from the ventromedial prefrontal cortex (PFC; Maier et al., 2006). Building upon this knowledge, the proposed research will determine how these mechanisms interact with the amygdala, a structure critical to anxiety states. The specific aims of this proposal will inform the basic understanding of how stress and coping affect anxiety on behavioral and neural levels and contribute to 3 of the 6 high-priority research areas of the NIMH Division of Neuroscience and Basic Behavioral Science. The aims have significant relevance to the Affect and Social Behavior program because the behavioral and neural components of stressor controllability and anxiety are similar to the condition in human PTSD patients. In these patients PFC activity is reduced and amygdala activity is increased, providing a mechanism for hyperanxiogenic responses to even mildly-emotional stimuli (Bremner et al., 1997). The results of this research could facilitate advancements in treatment, diagnosis and prevention of PTSD in humans. Research Design: In brief, rats will be exposed to a stressor and then tested for anxiety using a social exploration test. Social exploration is reduced under anxiogenic conditions. A variety of methods will be used to determine the contributions of selected brain nuclei, including: microinjection of excitatory or inhibitory compounds during stress, in vivo microdialysis, functional anatomy using retrograde tracing and immunohistochemistry for cellular activity markers. Together, these methods provide multiple levels of analysis of anxiety and the components of the neural systems that mediate the consequences of controllable or uncontrollable stressors. Relevance: According to NIMH publication OM-99 4157 (Revised), 3.6 % of American adults suffer from PTSD. Traumatic events include military conflict, hurricanes, acts of terrorism, illness, injury, physical abuse and criminal violence. However, these experiences do not leave all victims crippled with PTSD. The proposed research will provide critical insight to how the key psychological variable of coping contributes to the development or prevention of anxiety/PTSD after a traumatic event.

描述(由申请人提供)：先前的研究和人类文献表明，应对或控制感通常会减轻压力经历的后果，但在压力中缺乏或控制可能会导致病理性反应。在大鼠中，人们对调节可控和不可控应激源影响的基本神经机制知之甚多。重要的是，不可控的应激源引起5-羟色胺能中缝背核的激活，而可控的应激源通过来自腹内侧额叶皮质的抑制性调制来阻止这种激活(PFC；Maier等人，2006)。在这些知识的基础上，这项拟议的研究将确定这些机制如何与杏仁核相互作用，杏仁核是焦虑状态的关键结构。这项提案的具体目的将使人们对压力和应对如何影响行为和神经层面的焦虑有基本的理解，并有助于NIMH神经科学和基础行为科学分部6个高度优先研究领域中的3个。这些目标与情感和社会行为计划有重要的相关性，因为应激源的行为和神经成分的可控性和焦虑与人类创伤后应激障碍患者的情况相似。在这些患者中，PFC活动减少，杏仁核活动增加，为即使是轻微的情绪刺激也提供了一种高焦虑性反应的机制(Bremner等人，1997)。这一研究结果有助于促进人类创伤后应激障碍的治疗、诊断和预防的进步。研究设计：简而言之，大鼠将暴露在应激源中，然后使用社会探索测试来测试焦虑。在引起焦虑的情况下，社会探索性会减少。将使用多种方法来确定选定的大脑核团的贡献，包括：应激期间微量注射兴奋性或抑制性化合物，体内微透析，使用逆行示踪的功能解剖，以及细胞活性标记的免疫组织化学。总而言之，这些方法提供了对焦虑的多层次分析，以及调节可控或不可控应激源后果的神经系统组件。相关性：根据NIMH出版物OM-99 4157(修订版)，3.6%的美国成年人患有创伤后应激障碍。创伤性事件包括军事冲突、飓风、恐怖主义行为、疾病、伤害、身体虐待和刑事暴力。然而，这些经历并不会让所有的受害者都成为创伤后应激障碍的残废。这项拟议的研究将为应对的关键心理变量如何有助于创伤事件后焦虑/创伤后应激障碍的发展或预防提供关键的见解。