Neurobiology of Stress Inoculation

描述(申请人提供)：在心理健康研究中，压力的负面后果是公认的。然而，有趣的是，先前的压力暴露也与随后的韧性发展有关。之前的压力暴露促进了后续韧性的发展，这一概念被不同地描述为接种、免疫、钢化、增韧或茁壮成长，这一概念在拟议的研究中得到了检验，该研究使用阿普唑仑来减少压力接种的关键方面，这些方面被认为是培养韧性的。阿普唑仑是一种苯二氮卓类药物，可以减轻急性焦虑，减轻应激引起的下丘脑-垂体-肾上腺(HPA)轴的激活。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，引起焦虑的化合物育亨宾会激活HPA轴，加速条件性恐惧的习得性消退。这些发现与急性焦虑和HPA轴激活的认知和情绪处理促进应激相关精神障碍恢复的证据是一致的。这项拟议的研究验证了这样的假设，即急性焦虑和HPA轴的激活促进了应激接种诱导的弹性的发展。在每周应激接种训练之前，随机接受阿普唑仑或赋形剂对照组的动物与未接种阿普唑仑或赋形剂的动物进行比较，并在以后的年龄评估已建立的行为和神经内分泌弹性测量。如果急性焦虑的认知和情绪处理以及HPA轴的激活是发展应激接种诱导的复原力所必需的，那么在应激接种训练之前服用阿普唑仑的动物随后将类似于两种未接种治疗条件下的动物，与应激接种载体治疗条件相比，其复原力迹象减少。这项研究将扩大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复原力发展的预防性战略。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，并将有助于澄清在治疗干预过程中再次经历应激源的作用。这些问题之所以重要，是因为人们担心，重新经历应激源可能会加剧精神症状，阻碍康复，而不是促进复原力的发展。

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.