CRF Systems and Defensive Behavior

CRF 系统和防御行为

• 批准号: 6964566
• 负责人: ROBERT J BLANCHARD
• 金额: $ 10.18万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6964566
• 关键词: anxiety; autoradiography; biological models; conditioning; cooperative study; corticotropin releasing factor; fear; hormone metabolism; hormone regulation /control mechanism; interdisciplinary collaboration; laboratory mouse; minority institution research support; model design /development; neurobiology; neuroendocrine system; neurosciences; psychological defense mechanism; stress

This is a proposal to bring molecular techniques into a well-established behavioral/pharmacology laboratory at the University of Hawaii, in order to facilitate a research program on the relationship between CRF systems and anxiety-related behaviors and contribute to the development of Neurosciences research and training at this minority institution. This will involve the use of CRF receptor knock out mice, and, ex vivo analysis of regional brain receptor subtype occupancy associated with acidic astressin, in the context of two ethological procedures, the Mouse Defense Test Battery (MDTB), and the Rat Exposure Test (RET). These tests measure defensive behaviors that have been previously validated as selectively responsive to anxiolytic and panicolytic drugs. Based on preliminary findings, the potent CRF antagonist acidic astressin reduces specific defensive behaviors of these tests. The research program will extend these results and determine their mechanisms of action through use of agonists and antagonists at different CRF receptor subtypes. It will also evaluate the defensive behaviors of CRF receptor subtype knockout mice, developed by the Spiess laboratory, to verify these mechanisms. Ex vivo ligand binding and quantitative autoradiography will be used to determine CRF receptor occupancy following administration of acidic astressin at different dose levels, permitting evaluation of the relationship of receptor occupancy at these levels to their effects on particular defensive behaviors. These studies will thus utilize a range of new genetic and molecular techniques in analysis of the role of CRF systems in anxiety, enhancing understanding of these mechanisms and advancing the Neuroscience research capabilities of the University.

这是一项将分子技术引入夏威夷大学完善的行为/药理学实验室的提案，以促进 CRF 系统与焦虑相关行为之间关系的研究项目，并为神经科学研究和神经科学研究的发展做出贡献。在这个少数民族机构接受培训。这将涉及使用 CRF 受体敲除小鼠，以及在小鼠防御测试电池 (MDTB) 和大鼠暴露测试这两种行为学程序的背景下，对与酸性 astressin 相关的区域脑受体亚型占用进行离体分析（返回）。这些测试测量的是先前已被验证为对抗焦虑和恐慌药物有选择性反应的防御行为。根据初步发现，有效的 CRF 拮抗剂酸性 astressin 会降低这些测试的特定防御行为。该研究计划将扩展这些结果，并通过使用不同 CRF 受体亚型的激动剂和拮抗剂来确定其作用机制。它还将评估 Spiess 实验室开发的 CRF 受体亚型敲除小鼠的防御行为，以验证这些机制。体外配体结合和定量放射自显影将用于确定在不同剂量水平的酸性astressin施用后CRF受体占据，从而允许评估这些水平的受体占据与其对特定防御行为的影响的关系。因此，这些研究将利用一系列新的遗传和分子技术来分析 CRF 系统在焦虑中的作用，增强对这些机制的理解并提高大学的神经科学研究能力。