Development of Defensive Behavior and Social Stress Consequences

描述（由申请人提供）：社会压力对一生的身心健康都有不利影响，其影响可能与青春期特别相关，因为这是大脑回路大量生长和重组的时期。迄今为止，大多数关于社会压力的行为和生理后果的基础研究都集中在成年雄性啮齿动物身上。本研究采用一种大鼠社会压力模型，即“居民-入侵者模型”，来描述与成年期相比，青春期不同发展阶段对社会压力的神经行为反应及其后果。这项研究还承担了一个重要的挑战，即调查性别差异对社会压力及其后果的反应。这里提出的研究方案是基于初步数据表明，防御性下属反应的侵略性同物发展从青春期到成年。与此相关的是，在应对后续挑战时，人们不再采取积极的应对策略。这些与年龄相关的行为差异与蓝斑（LC）神经元活动的明显变化有关。因此，这一建议验证了一个中心假设，即青春期早期的社会压力破坏了调节下属防御行为发展的特定神经通路的个体发育，这种破坏对青春期的行为和认知产生影响，并持续到成年。这一假设将在三个具体目标中得到检验。目的1将使用功能神经解剖学方法识别和比较青春期和成年期不同阶段受社会压力影响的神经回路，并检查与社会行为和压力相关的肽系统的变化。目的2将描述和比较青春期和成年期不同阶段LC神经元对社会压力的反应。目的3将检查青少年时期社会压力的具体行为和认知后果，并评估这些影响的持久性。由于在Aims 1和Aims 2中研究的一些神经基质与AIM 3中测试的行为终点有关，因此本研究旨在揭示在特定发展时期参与社会压力初始反应（防御行为）的神经基质和回路如何在决定随后的急性和长期社会压力后果中发挥作用。总之，拟议的研究将提供关于防御行为和社会压力后果的发育和性别差异的关键信息。鉴于社会压力对心理健康的影响，这些研究将促进我们对人类精神疾病发展的理解，以及对这些疾病发病和病因的性别差异的神经生物学基础的理解。)

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.)