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。

基本信息

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
项目类别：
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

项目摘要

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，应对或控制感知通常会减轻压力经历的后果，但是压力期间缺乏或控制可能会导致病理反应。在大鼠中，对介导可控制和不可控制的应激源的影响的基本神经机制知之甚少。重要的是，不可控制的应激源会导致血清素能的背部raphe核激活，而可控的应激源则可以通过腹侧前额叶皮层抑制性调节来阻止这种激活（PFC; Maier等，2006）。在这些知识的基础上，拟议的研究将确定这些机制如何与杏仁核相互作用，杏仁核是对焦虑状态至关重要的结构。该提案的具体目的将为压力和应对如何影响对行为和神经水平的焦虑的基本理解，并为NIMH神经科学和基本行为科学的NIMH分区的6个高优先性研究领域中的3个做出了贡献。该目标与情感和社会行为计划具有很大的相关性，因为压力源可控性和焦虑的行为和神经成分与人类PTSD患者的状况相似。在这些患者中，PFC活性降低并增加了杏仁核活性，从而为甚至对轻度情感刺激的高抗反应反应提供了一种机制（Bremner等，1997）。这项研究的结果可以促进人类治疗，诊断和预防PTSD的进步。研究设计：简而言之，大鼠将暴露于压力源，然后使用社会勘探测试对焦虑进行测试。在焦虑症状况下，社会探索减少了。将使用多种方法来确定选定的脑核的贡献，包括：应激期间的兴奋性或抑制性化合物，体内微透析，使用逆行痕迹的功能解剖结构以及用于细胞活性标记的免疫组织化学。这些方法共同提供了焦虑和神经系统组成部分的多个级别，这些分析介导了可控或不可控制的压力源的后果。相关性：根据NIMH出版物OM-99 4157（修订），3.6％的美国成年人患有PTSD。创伤事件包括军事冲突，飓风，恐怖主义行为，疾病，伤害，身体虐待和犯罪暴力。但是，这些经历并没有使所有受害者因PTSD而瘫痪。拟议的研究将为应对的关键心理变量如何促进创伤事件后的焦虑/PTSD的发展或预防。