COGNITIVE AND PHARMACOLOGICAL MODULATION OF THE HUMAN NEUROENDOCRINE STRESS AXIS

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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.'