Development of Defensive Behavior and Social Stress Consequences

描述（由申请人提供）：社会压力对整个生命的身心健康产生不利影响，其影响可能在青春期特别相关，因为这是大脑回路大幅增长和重组的时期。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。拟议的研究使用大鼠社会压力模型，“居民-入侵者模型”，以描述与成年期相比，青少年发育不同阶段对社会压力的神经行为反应和后果。这项研究还承担了调查社会压力反应或其后果的性别差异的重要挑战。这里提出的研究计划是基于初步的数据表明，防御从属反应的攻击性同种发展整个青春期到成年。在时间上与此相关的是，为应对随后的挑战，人们不再采取积极的应对战略。这些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，这项建议测试的核心假设，即社会压力在青春期早期扰乱了个体发育的特定神经通路的重要性，调节发展的从属防御行为，这种破坏有影响的行为和认知在青春期持续到成年。这一假设将在三个具体目标中得到检验。目标1将使用功能神经解剖学方法识别和比较青少年和成年期不同阶段社会压力所涉及的神经回路，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LC神经元在青春期和成年期的不同阶段对社会应激的反应。目标3将研究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。由于目标1和目标2中研究的一些神经基质与目标3中测试的行为终点有关，因此组织这些研究是为了揭示在发育的特定时间对社会压力（防御行为）的初始反应中涉及的神经基质和回路如何在确定社会压力的后续急性和长期后果中发挥作用。总之，拟议的研究将提供有关防御行为和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，这些研究将促进我们对人类精神疾病发展的理解，以及这些疾病发病和病因的性别差异的神经生物学基础。

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.)