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

• 批准号: 7660781
• 负责人: Royce Lee
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-22 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660781
• 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

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）：该R21项目拟开发一种适用于临床研究的中枢促肾上腺皮质激素释放激素（CRH）受体功能的新型药理学-脑电图探针。这项工作的长期目标是一种基于机制的治疗压力相关精神疾病的方法。血脑屏障对 CRH 的相对不渗透性是测试有关人类中枢 CRH 功能的机械理论的障碍。这项工作的新颖性在于将 CRH 神经肽施用到嗅觉上皮，以定量测试鼻内施用 CRH 在健康对照和缓解抑郁症患者中的药效学和药代动力学特性。我们的目标是对 1. 鼻内和 2. 静脉 CRH 进行两项平行、安慰剂交叉药效学研究。我们主要感兴趣的是鼻内 CRH（与安慰剂相比）对大脑活动（事件相关脑电图）和惊吓反射 (EMG) 定量测量的影响。我们实验室的初步人体数据与这种效应一致。该研究与公共卫生的相关性有两个方面。首先，获得 CRH 功能的药效学探针将有助于抑郁症的机制研究。其次，药效学读数 CRH 功能可能有助于定量指导未来基于抗 CRH 受体的治疗。公共卫生相关性：该 R21 提案的目的是测试健康成年男性和女性受试者中枢 CRH 受体功能的探针。该探头将鼻内 CRH 激发与脑皮层活动的脑电图测量结合起来。为了了解鼻内探针的动力学，还将进行静脉内 CRH 激发，以提供比较数据。