Neurobiology of Stress Inoculation

描述（由申请人提供）：在心理健康研究中，压力的负面影响是公认的。然而，有趣的是，先前的压力暴露也与随后的恢复力发展有关。不同的描述为接种，免疫，钢铁，增韧，或蓬勃发展，先前的压力暴露促进了随后的弹性发展的概念在拟议的研究中得到了测试，使用阿普唑仑来减少被认为可以培养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，可减少急性焦虑，减轻下丘脑-垂体-肾上腺（HPA）轴因压力而激活。在动物模型中，苯二氮卓类药物也会干扰习得的条件恐惧消退。相反，致焦虑化合物育亨宾激活下丘脑中轴，加速习得性消除条节性恐惧。这些发现与急性焦虑的认知和情绪加工和HPA轴激活促进应激相关精神障碍的恢复的证据一致。本研究验证了急性焦虑和HPA轴激活促进应激接种诱导弹性发展的假设。在每周的应激接种训练之前，随机分配接受阿普唑仑或媒介对照的动物与未接种阿普唑仑或媒介对照的动物进行比较，并在年龄较大时评估既定的行为和神经内分泌测量的恢复力。如果急性焦虑的认知和情绪加工和HPA轴的激活对于应激接种诱导的恢复能力的发展是必要的，那么在应激接种训练前给予阿普唑仑的动物随后与未接种治疗条件下的动物相似，并且与应激接种治疗条件下的动物相比，恢复能力的迹象减少。这项研究将扩展我们对增强心理健康能力的理解，其目标是推进旨在最有效地促进复原力发展的预防策略。这些研究的结果也将提供关于苯二氮卓类药物是否辅助或干扰行为治疗的见解，并将有助于阐明在治疗干预过程中重新体验压力源的作用。这些问题很重要，因为人们担心再次经历压力源可能会加剧精神症状，阻碍康复，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.