Neurobiology of Stress Inoculation

描述（由申请人提供）：压力的负面后果在心理健康研究中得到了广泛认可。然而，有趣的是，先前的压力暴露也与随后的弹性发展有关。不同的描述为免疫，免疫，钢铁，韧化，或蓬勃发展的概念，即先前的压力暴露促进后续弹性的发展，在拟议的研究中使用阿普唑仑进行测试，以减少被认为是促进弹性的压力接种的关键方面。阿普唑仑是一种苯二氮卓类药物，可减轻急性焦虑，并减弱应激引起的下丘脑-垂体-肾上腺（HPA）轴激活。在动物模型中，苯二氮卓类药物也会干扰条件性恐惧的习得性消退。相反，致焦虑化合物育亨宾激活HPA轴，加速条件性恐惧的习得性消退。这些发现与急性焦虑的认知和情绪处理以及HPA轴激活促进应激相关精神障碍恢复的证据一致。该研究验证了急性焦虑和HPA轴激活促进应激接种诱导的复原力发展的假设。将在每个每周应激接种训练期之前随机接受阿普唑仑或媒介物对照的动物与施用阿普唑仑或媒介物的未接种动物进行比较，并在以后的年龄对建立的恢复力的行为和神经内分泌测量进行评估。如果急性焦虑和HPA轴激活的认知和情感处理对于应激接种诱导的恢复力的发展是必要的，则在应激接种训练期之前给予阿普唑仑的动物随后将类似于来自两种未接种处理条件的动物，与应激接种媒介物处理条件相比，恢复力的指示减弱。这项研究将扩展我们对增强心理健康能力的理解，目标是推进旨在最有效地促进恢复力发展的预防性策略。这些研究的结果还将提供关于苯二氮卓类药物是否有助于或干扰行为治疗的见解，并将有助于澄清治疗干预期间重新经历压力源的作用。这些问题很重要，因为人们担心重新经历压力源可能会加剧精神症状，阻碍恢复，而不是促进恢复力的发展。

DESCRIPTION (provided by applicant): The negative consequences of stress are well-recognized in mental health research. Interestingly, however, prior stress exposure has also been linked to the subsequent development of resilience. Variously described as inoculating, immunizing, steeling, toughening, or thriving, the notion that prior stress exposure facilitates the development of subsequent resilience is tested in the proposed research using alprazolam to diminish key aspects of stress inoculation that are thought to foster resilience. Alprazolam is a benzodiazepine medication that reduces acute anxiety and attenuates hypothalamic-pituitary-adrenal (HPA) axis activation by stress. In animal models, benzodiazepines also interfere with learned extinction of conditioned fear. Conversely, the anxiogenic compound yohimbine activates the HPA axis and accelerates learned extinction of conditioned fear. These findings are consistent with evidence that cognitive and emotional processing of acute anxiety and HPA axis activation promote recovery from stress-related psychiatric disorders. The proposed research tests the hypothesis that acute anxiety and HPA axis activation facilitate the development of stress inoculation-induced resilience. Animals randomized to receive alprazolam or the vehicle control before each weekly stress inoculation training session are compared to non-inoculated animals administered alprazolam or vehicle and assessed at later ages on established behavioral and neuroendocrine measures of resilience. If cognitive and emotional processing of acute anxiety and HPA axis activation are necessary for the development of stress inoculation-induced resilience, then animals administered alprazolam before stress inoculation training sessions will subsequently resemble animals from both non-inoculated treatment conditions with diminished indications of resilience compared to the stress inoculated vehicle treatment condition. This research will extend our understanding of the capacity for enhancing mental health, with the goal of advancing preventative strategies designed to most efficiently foster the development of resilience. Results from these studies will also provide insights on whether benzodiazepines aid or interfere with behavioral therapies, and will help to clarify the role of re-experiencing stressors during therapeutic interventions. These issues are important because of concerns that re-experiencing stressors may exacerbate psychiatric symptoms and impede recovery instead of fostering the development of resilience.