The Effect of Corticotropin Releasing Hormone on Cortical Arousal

促肾上腺皮质激素释放激素对皮质唤醒的影响

基本信息

批准号：
7809650
负责人：
Royce Lee
金额：
$ 19.25万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-22 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7809650
关键词：
Accounting Acoustics Adult Anger Arousal Blood - brain barrier anatomy Blood Circulation Brain CNS processing Characteristics Clinical Clinical Research Clinical Treatment Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Receptors Cross-Over Studies Data Depressive disorder Diagnostic Discrimination Dose Double-Blind Method Drug Kinetics Due Process Electroencephalogram Emotions Event Exhibits Face Female Frequencies Future Human Image Intravenous Investigation Kinetics Laboratories Measurement Measures Mediating Mediation Mental disorders Modeling Neuropeptides Noise Olfactory Epithelium Pharmaceutical Preparations Pharmacodynamics Phase Placebos Process Property Psychiatry Randomized Reflex action Relative (related person)Role Saline Signal Transduction Stimulus Stress Testing Visual Work base cost depressive symptoms human data interest male novel novelty processing prognostic public health relevance receptor function relating to nervous system research study response theories trait visual stimulus

项目摘要

DESCRIPTION (provided by applicant): This R21 project proposes to develop a novel pharmacological-EEG probe of central corticotropin- releasing hormone (CRH) receptor function suitable for clinical research. The long-term objective of this work is a mechanism-based treatment approach to stress related psychiatric disorders. The relative impermeability of the blood brain barrier to CRH is an obstacle to testing mechanistic theories regarding central CRH function in humans. The novelty of this work lies in its administration of the CRH neuropeptide to the olfactory epithelium in order to quantitatively test pharmacodynamic and pharmacokinetic properties of intranasally administered CRH in healthy controls and remitted depressives. We aim to conduct two parallel, placebo-crossover pharmacodynamic studies of 1. intranasal and 2. intravenous CRH. We are primarily interested in the effect of intranasal CRH (vs. placebo) on a quantitative measurement of brain activity (event related EEG) and startle reflex (EMG). Preliminary human data from our laboratory are consistent with such effects. The public health relevance of the study is two-fold. Firstly, obtaining a pharmacodynamic probe of CRH function will permit mechanistic investigations of depressive disorder. Secondly, a pharmacodynamic readout CRH function may help to quantitatively guide future anti-CRH receptor based treatments. PUBLIC HEALTH RELEVANCE: The objective of this R21 proposal is to test a probe of central CRH receptor function in healthy adult male and female subjects. The probe combines intranasal CRH challenge with EEG measures of brain cortical activity. In order to understand the kinetics of the intranasal probe, an intravenous CRH challenge will also be performed, to provide comparison data.

描述（由申请人提供）：这个R21项目提议开发一种新型的药理学 - EEG探针，用于中枢性皮质激素 - 释放激素（CRH）受体功能，适用于临床研究。这项工作的长期目的是一种基于机制的治疗方法，用于与压力相关的精神疾病。血脑屏障与CRH的相对不渗透性是测试有关人类中央CRH功能的机械理论的障碍。这项工作的新颖性在于它将CRH神经肽施用到嗅觉上皮，以定量测试在健康对照组中鼻内施用的CRH的药效学和药代动力学特性，并使抑郁症降低。我们的目标是进行两项平行的安慰剂 - 交叉药效学研究，对1。1。我们主要对鼻内CRH（与安慰剂）对大脑活动（事件相关的EEG）和惊吓反射（EMG）的影响感兴趣。来自我们实验室的初步人类数据与此类效果一致。该研究的公共卫生相关性是两个方面。首先，获得CRH功能的药效学探针将允许对抑郁症的机械研究。其次，药效学读数CRH功能可能有助于定量指导未来的抗CRH受体治疗。公共卫生相关性：该R21提案的目的是测试健康的成年男性和女性受试者中心CRH受体功能的探测。该探针将鼻内CRH挑战与脑皮层活性的脑电图测量结合在一起。为了了解鼻内探针的动力学，还将进行静脉内CRH挑战，以提供比较数据。