Neuroendocrine Consequences of Two Animal Models of Active Behavioral Coping

描述（由申请人提供）：拟议实验的总体目标是检查下丘脑-垂体-甲状腺（HPT）轴的急性应激调节，并确定主动行为应对模型是否可以改善应激对神经内分泌系统和行为的影响。HPT轴作为应激反应系统尚未得到很好的研究，但它具有重要的生理影响，包括情绪和情感状态的变化。成功应对压力是必要的，以促进个人的弹性和防止病理结果与压力暴露。确定成功应对的神经和内分泌后果是至关重要的。以前很少有研究积极行为应对对急性应激引起的甲状腺激素下降的影响。有趣的是，我们有初步证据表明，急性不可避免的压力会导致外周甲状腺激素水平下降，而且，这种压力引起的下降在能够通过逃避压力源来应对的动物身上有所减少。在这项拨款申请中，我们建议全面评估急性应激时HPT轴的活动，并确定积极的行为应对策略是否能防止应激引起的HPT轴活动下降。我们将重点关注的两种积极的行为应对策略是：1。通过操作性反应逃离/控制压力源（尾震）。在压力源作用下的位移行为（咀嚼木棍）的表现。此外，我们建议确定积极行为应对对受压力负面影响的社会行为的影响。最后，下丘脑-垂体-肾上腺（HPA）轴是一个非常明确的应激反应系统，但位移行为的表现对HPA轴的应激激活的影响尚未完全表征。为了确定应激引起的HPA和HPT轴的变化，我们将测量循环激素水平和下丘脑mRNA和hnRNA水平。拟议研究的实验动物是成年雄性大鼠。HPT轴具有已知的外周和中枢作用，以及明确的神经解剖学输入。尽管有这些知识，这种神经内分泌系统在应激反应方面的研究相对较少。本R03申请中提出的研究将证实并扩展我们对HPT轴对压力的反应和主动行为应对的理解。此外，它们将为未来研究HPT轴应激调节的神经基础特征以及确定这种神经调节如何被主动行为应对所改变提供基础。公共卫生相关性：成功应对生活压力源对于预防由压力暴露引起的负面健康结果至关重要。啮齿动物模型具有与人类相似的反应系统，可以用来直接识别压力的负面后果，也可以用来识别成功应对压力的后果。这些系统的识别可以为人类提供成功的压力应对策略、干预和治疗方法。

DESCRIPTION (provided by applicant): The overall goals of the proposed experiments are to examine acute stress regulation of the hypothalamic-pituitary-thyroid (HPT) axis and to determine if models of active behavioral coping can ameliorate stress effects on neuroendocrine systems and behavior. The HPT axis has not been well studied as a stress responsive system, but has important physiological consequences, including changes in mood and affective states. Successful coping with stress is necessary to promote individual resiliency and to prevent pathological outcomes associated with stress exposure. It is essential to determine the neural and endocrine consequences of successful coping. There is little previous work examining the impact of active behavioral coping on acute stress-induced decreases in thyroid hormones. Interestingly we have preliminary evidence that acute inescapable stress can cause a decrease in peripheral thyroid hormones levels and, moreover, that this stress-induced decrease is diminished in animals that can cope with, via escaping, the stressor. In this grant application we propose to fully assess the activity of the HPT axis during acute stress, and also determine if active behavioral coping strategies prevent stress-induced decreases in HPT axis activity. The two active behavioral coping strategies that we will focus on are 1. Escaping/controlling the stressor (tail-shock) via an operant response and 2. Performance of a displacement behavior (chewing a wooden stick) during the stressor. In addition, we propose to determine the effects of active behavioral coping on social behaviors that are negatively impacted by stress. Finally, the hypothalamic-pituitary-adrenal (HPA) axis is a very well characterized stress-responsive system, but the impact of the performance of a displacement behavior on stress activation of the HPA axis has not been completely characterized. To determine stress- induced changes in the HPA and HPT axes, we will measure both circulating hormone levels and hypothalamic mRNA and hnRNA levels. The experimental animal for the proposed studies is the adult male rat. The HPT axis has known peripheral and central effects, and well-defined neuroanatomical inputs. Despite this knowledge, this neuroendocrine system is relatively unstudied within the context of stress responsiveness. The studies proposed in this R03 application will confirm and extend our understanding of the HPT axis responses to stress and active behavioral coping. Further, they will provide the foundation for future studies characterizing the neural underpinnings of stress regulation of the HPT axis and determining how this neural regulation is altered by active behavioral coping. PUBLIC HEALTH RELEVANCE: Successful coping with life stressors is critical for preventing negative health outcomes caused by stress exposure. Rodent models have analogous response systems to people and can be used to directly identify negative consequences of stress and also consequences of successful stress coping. Identification of these systems may provide insight into successful stress-coping strategies, interventions, and therapies for humans.