STRESS REACTIVITY--NEUROCHEMISTRY OF INDIV DIFFERENCES

应激反应--个体差异的神经化学

• 批准号: 3475311
• 负责人: ROBERT C. DRUGAN
• 金额: $ 10.7万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3475311
• 关键词: GABA receptor; anxiety; autoradiography; behavior; benzodiazepine receptor; coping; depression; disease /disorder model; laboratory rat; learned helplessness; ligands; muscimol; neurochemistry; neuropharmacology; radionuclides; receptor binding; stress; tritium

Learned helplessness has been proposed to be an animal model of depresion. Much research has dealt with the physiological and biochemical changes associated with this syndrome. Recently, behavioral pharmacology experiments have suggested that anxiety and its biological correlates may play a role in the development of learned helplessness. To date, little work has examined central "anxiety sites" and their relationship with this syndrome or with individual differences in stress reactivity. We propose to carry out in vitro radioligand (homogenate) binding and autoradiography, in vivo behavioral pharmacology and in vivo receptor binding analysis in rats to ascertain the involvement of the central benzodiazepine/GABA receptor complex and its relationship to depression in rats. These experiments will not only test the hypothesis that the benzodiazepine/GABA receptor is differentially modulated by active coping behavior (stress control) and depression, but more importantly, will examine if this site is an important link in hypothesized continuum between anxiety and the development of full-blown depression. We will employ a recently developed prescreening procedure to provide 2 behaviorally "homogeneous" populations of stress-sensitive (helpless) and stress-resilient (coping) rats. Once these two populations have been identified, their pharmacological and neuro-chemical responsivity to an inescapable stressor will be characterized. Initial stress-induced changes in these sites may predict future individual differences in stress responsivity. The proposed experiments will provide preclinical evidence concerning both in vitro and functional changes of a site thought to be involved in the physiology of anxiety and how these changes correlate with active coping behavior and depression. This site will be tested for its sensitivity in predicting future stress vulnerability or resistance. The heuristic value of using animal models of psychopathology is to allow for the development of new diagnostic criteria for initiating earlier, more effective treatment for such disorders as depression. This work will aid in the development of both behavioral therapy and pharmacotherapy for stress-related disorders in humans.

已经提出学习的无助是一种动物模型 疏度。 很多研究都涉及生理和 与该综合征相关的生化变化。 最近，行为 药理学实验表明焦虑及其生物学 相关性可能会在学习的无助的发展中发挥作用。 迄今为止，很少的工作检查了中心的“焦虑场所”及其 与该综合征或压力的个体差异的关系 反应性。 我们建议进行体外放射性（匀浆）结合和 放射自显影，体内行为药理学和体内受体 大鼠的结合分析以确定中央的参与 苯二氮卓/GABA受体复合物及其与抑郁的关系 在老鼠中。 这些实验不仅会检验 苯二氮卓/GABA受体通过主动应对差异调节 行为（压力控制）和抑郁，但更重要的是， 检查该站点是否是假设连续体的重要链接 在焦虑与成熟抑郁症的发展之间。 我们将采用最近开发的预筛选程序来提供2 在行为上“同质”的压力敏感（无助）和 应力弹性（应对）大鼠。 一旦这两个人口 确定，它们的药理和神经化学反应性 不可避免的应激源将被表征。 初始应力引起的 这些站点的变化可能会预测未来的个体差异 压力反应性。 提出的实验将提供有关临床前证据 被认为涉及的站点的体外和功能变化 焦虑的生理以及这些变化与主动 应对行为和抑郁。 该网站将经过测试 在预测未来的压力脆弱性或抵抗力方面的敏感性。 这 使用心理病理动物模型的启发式价值是允许 开发新的诊断标准以较早发起，更多 有效治疗抑郁症等疾病。 这项工作将有助于 在开发行为疗法和药物治疗方面 人类与压力有关的疾病。