Development of Defensive Behavior and Social Stress Consequences

防御行为的发展和社会压力后果

基本信息

批准号：
8660915
负责人：
SEEMA BHATNAGAR
金额：
$ 10万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8660915
关键词：
Acute Address Adolescence Adolescent Adolescent Development Adult Aggressive behavior Anxiety Arousal Basic Science Behavior Behavioral Brain Cognition Cognitive Complement Coping Behavior Data Development Disease Etiology Female Fright Future Growth Human Life Light Mediating Mediator of activation protein Mental Depression Mental Health Mental disorders Modeling Mood Disorders Neural Pathways Neuroanatomy Neurobiology Neurons Norepinephrine Odors Peptides Phenotype Physiological Play Rattus Research Rodent Role Sex Characteristics Shapes Social Behavior Social Interaction Staging Stimulus Stress Stress and Coping System Testing Time adverse outcome affiliative behavior age related base biological adaptation to stress cognitive function coping early adolescence locus ceruleus structure male neural circuit neurobehavioral neurobiological mechanism neurodevelopment norepinephrine system physical conditioning programs relating to nervous system response sex social social stress

项目摘要

DESCRIPTION (provided by applicant): Social stress has adverse consequences for physical and mental health throughout life and its impact may be particularly relevant during adolescence as this is a time of substantial growth and reorganization of brain circuits. To date, most basic research into the behavioral and physiological consequences of social stress has focused on adult male rodents. The proposed research uses a model of rat social stress, "the resident- intruder model", to characterize the neurobehavioral responses to, and consequences of, social stress at different stages of adolescent development compared to adulthood. This research also takes on the important challenge of investigating sex differences in the response to social stress or its consequences. The research program proposed here is based on preliminary data indicating that the defensive subordinate response to an aggressive conspecific develops throughout adolescence into adulthood. Temporally correlated to this is a shift away from active coping strategies in response to subsequent challenges. These age-related behavioral differences are associated with distinct changes in locus coeruleus (LC) neuronal activity. Therefore, this proposal tests the central hypothesis that social stress in early adolescence disrupts the ontogeny of specific neural pathways important for regulating the development of subordinate defensive behaviors and that this disruption has effects on behavior and cognition in adolescence that endure into adulthood. This hypothesis will be tested in three specific Aims. Aim 1 will identify and compare neural circuits engaged by social stress at different stages of adolescence and in adulthood using a functional neuroanatomy approach and examining changes in peptide systems related to social behavior and stress. Aim 2 will characterize and compare responses of LC neurons to the social stress at different stages of adolescence and in adulthood. Aim 3 will examine specific behavioral and cognitive consequences of social stress during adolescence and evaluate the endurance of these effects. Because some of the neural substrates being investigated in Aims 1 and 2 have been implicated in the behavioral endpoints being tested in AIM 3, the studies are organized to reveal how the neural substrates and circuits involved in the initial response to social stress (the defensive behaviors) at a particularly time in development play a role in determining the subsequent acute and long-term consequences of social stress. Together, the proposed studies will provide critical information about developmental and sex differences in defensive behaviors and in the consequences of social stress. Given the impact of social stress on mental health these studies will advance our understanding of the development of psychiatric disorders in humans and on the neurobiological basis for gender differences in the onset and etiology of these diseases.)

描述（由申请人提供）：社会压力对整个生命的身体和心理健康及其影响在青春期可能特别相关，因为这是大脑回路的实质性增长和重组的时期。迄今为止，对社会压力的行为和生理后果的大多数基础研究都集中在成年男性啮齿动物上。拟议的研究使用了一种大鼠社会压力模型，即“居民入侵者模型”，以表征与成年相比，在青少年发展不同阶段社会压力的神经行为反应和后果。这项研究还面临着调查对社会压力或其后果的性别差异的重要挑战。此处提出的研究计划基于初步数据，表明对积极特异性的防御性下属反应在整个青春期至成年期都会发展。与此相关的时间相关是从积极的应对策略中转变，以应对随后的挑战。这些与年龄相关的行为差异与基因座（LC）神经元活性的不同变化有关。因此，该提案检验了一个中心假设，即青春期早期的社会压力破坏了对调节下属防御行为发展重要的特定神经途径的个体发育，并且这种破坏对持续到成年的青春期行为和认知的影响。该假设将以三个特定目的进行检验。 AIM 1将使用功能性神经解剖学方法来识别和比较在青春期和成年期间社会压力与社会压力所吸引的神经回路，并检查与社会行为和压力有关的肽系统的变化。 AIM 2将表征和比较LC神经元在青春期和成年期的不同阶段对社会压力的反应。 AIM 3将检查青春期社会压力的特定行为和认知后果，并评估这些影响的耐力。由于AIM 1和2中研究的某些神经底物已与AIM 3中测试的行为终点有关，因此进行了研究，以揭示如何在开发中对社会压力（防御行为）最初反应（防御行为）的最初响应中涉及的神经底物和循环如何在确定随后的急性急性和长期压力中发挥作用。拟议的研究将共同提供有关防御行为以及社会压力后果的发展和性别差异的关键信息。鉴于社会压力对心理健康的影响，这些研究将使我们对人类精神疾病的发展以及这些疾病发作和病因的性别差异的神经生物学基础的理解。）