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: 7918261
• 负责人: John Paul Christianson
• 金额: $ 3.51万
• 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 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7918261
• 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; 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; 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; activity marker; classical conditioning; conditioned fear; coping; 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体验的后果，但在压力期间缺乏控制可能会导致病理反应。在大鼠中，人们对调节可控和不可控压力的基本神经机制了解很多。重要的是，不可控制的应激源引起多巴胺能中缝背核的激活，而可控制的应激源通过来自腹内侧前额叶皮质的抑制性调节来防止这种激活（PFC; Maier等人，2006年）。基于这些知识，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。该提案的具体目标将告知压力和应对如何影响行为和神经层面的焦虑的基本理解，并有助于神经科学和基础行为科学的NIMH部门的6个高优先级研究领域中的3个。这些目标与情感和社会行为项目有着重要的相关性，因为压力源可控性和焦虑的行为和神经成分与人类PTSD患者的情况相似。在这些患者中，PFC活性降低，杏仁核活性增加，提供了对甚至轻微情绪刺激的过度焦虑反应的机制（Bremner等人，1997年）。这项研究的结果可以促进人类PTSD治疗，诊断和预防的进步。研究设计：简而言之，大鼠将暴露于压力源，然后使用社会探索测试测试焦虑。社会探索在焦虑状态下减少。将使用各种方法来确定所选择的脑核团的贡献，包括：在应激过程中显微注射兴奋性或抑制性化合物，体内微透析，使用逆行追踪和免疫组织化学细胞活性标记的功能解剖。总之，这些方法提供了多层次的分析焦虑和神经系统的组成部分，介导可控或不可控的压力源的后果。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受害者都患上创伤后应激障碍。拟议的研究将提供关键的洞察力如何应对的关键心理变量有助于创伤事件后焦虑/PTSD的发展或预防。