COGNITIVE AND PHARMACOLOGICAL MODULATION OF THE HUMAN NEUROENDOCRINE STRESS AXIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究项目将有助于我们理解大脑如何调节我们对压力的反应中涉及的荷尔蒙和行为。我们将探索一种特殊的荷尔蒙，称为缩胆囊素，在帮助控制其他荷尔蒙的释放方面所起的自然作用。我们还将探索可能影响这种荷尔蒙释放的心理因素的作用。参与者将是一组没有特别焦虑、抑郁或压力相关障碍问题的人。将有大约60名年龄在18岁到45岁之间的受试者，他们的身体健康，没有服用药物或药物。受试者将在两个下午进入密歇根大学医院的综合临床研究中心。他们将在手臂的静脉中放置一条静脉导管，持续大约4个小时。我们将通过这条线抽取血液样本，并将使用它来给他们注射一种名为五胃泌素的药物或安慰剂(非活性物质)输液。五肽胃泌素是消化激素胃泌素和胆囊收缩素的合成版，可以刺激体内某些细胞释放其他激素。我们最感兴趣的是皮质醇和促肾上腺皮质激素，这两种激素的释放是由五肽胃泌素触发的，人们在试图应对挑战或压力时也会分泌这两种激素。我们将使用不同类型的指令来研究思想和感觉如何影响这些荷尔蒙的释放。受试者收到的指令将随机确定。这项研究可能有助于我们更好地了解缩胆囊素和心理因素在人类应激反应系统中的作用。我们希望这项工作将有助于制定更好的压力管理办法。我们还希望它将帮助我们开发出对研究人类在不同精神障碍中的应激反应系统有用的模型，并可能帮助我们寻找其中一些障碍的原因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research project will contribute to our understanding of how the brain regulates the hormones and behaviors involved in our responses to stress. We will be exploring the natural role of a specific hormone, called cholecystokinin, in helping to control the release of other hormones. We will also be exploring the role of psychological factors that might effect this hormone release. Participants will be a "control group" of people who do not have particular problems with anxiety, depression, or stress-related disorders. There will be about 60 subjects between 18 and 45 years of age, who are medically healthy and are not taking medication or drugs. Subjects will be admitted on two afternoons to the General Clinical Research Center at the University of Michigan Hospital. They will have an intravenous line in place in a vein in their arm for about 4 hours. We will draw blood samples through this line and will also use it to give them either a dose of a medication called pentagastrin or a placebo (inactive substance) infusion. Pentagastrin is a synthetic version of the digestive hormones gastrin and cholecystokinin, which can stimulate the release of other hormones from certain cells in the body. We will be most interested in cortisol and adrenocorticotropin, two hormones whose release is triggered by pentagastrin and that people also secrete when attempting to cope with a challenge or stressor. We will be using different types of instructions to also study how thoughts and feelings can effect release of these hormones. Which instructions subjects receive will be determined randomly. The study may help us better understand the role of cholecystokinin and psychological factors in human stress response systems. We hope this work will contribute to the development of improved approaches to the management of stress. We also hope that it will help us to develop models that will be useful in studying the human stress response system in different psychiatric disorders and perhaps help us search for the causes of some of these disorders.