ETHOPHARMACOLOGICAL APPROACH TO THE STUDY OF ANXIETY

焦虑研究的民族药理学方法

• 批准号: 6240067
• 负责人: DIXIE CAROLINE BLANCHARD
• 金额: $ 1.52万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240067
• 关键词: NMDA receptors; anxiety; behavior; behavior test; behavioral /social science research tag; benzodiazepine receptor; benzodiazepines; body movement; cholecystokinin; corticotropin releasing factor; drug interactions; escape reaction; ethology; fear; gender difference; laboratory rat; neuropharmacology; psychological defense mechanism; serotonin; stress

A recently developed animal model for evaluation of anxiolytic and anxiogenic compounds involves two test batteries that elicit and measure defensive reactions to the presence of threat stimuli (Fear/Defense Test Battery), or to potential threat (Anxiety/Defense Test Battery). Present threat stimuli elicit flight, freezing, defensive threat and defensive biting, while freezing, risk assessment and the inhibition of nondefensive behavior are seen to partial predatory stimuli or places where predators have been seen. Because these tests do not use painful stimuli or involve learning of reactions to stimuli associated with pain, they are analytically less complex than traditional anxiety models, but provide a full range of defense behaviors for analysis of bidirectional change associated with administration of pharmacological compounds. Work completed with benzodiazepines, 5-HT ligands and imipramine suggests that drugs with clinical efficacy against anxiety produce specific patterns of change in risk assessment and inhibition of nondefensive behavior, found also with the NMDA antagonist MK-801, but not with morphine, scopolamine, or alprazolam. In contrast, the panickogenic agent yohimbine reduced freezing and enhanced flight and avoidance, suggesting a relationship between these behaviors and the target symptoms of panic attack. An additional feature emerging from this work is the consistent finding of gender differences in defensive behaviors and in sensitivity to anxiolytic drugs, in these rodent models. The proposed program will use these test batteries, plus tests of antipredator vocalization and analysis which differentiates anxiolytic and sedative profiles, to investigate patterns of effect for benzodiazepine receptor partial agonists, additional 5-HT ligands, and 3 classes of compounds with novel actions (CCK, CRF and NMDA ligands), including additional panickogenic agents. This program will provide a much finer analysis of the pharmacology of the neurobehavioral defense systems that has previously been available, and will additionally permit an analysis of gender effects in defensive behaviors linked to anxiety, and in reactions to different classes of anxiolytic drugs.

最近开发的用于评估抗焦虑和抗抑郁作用的动物模型 引起焦虑的化合物涉及两个测试电池，它们引发并测量 对威胁刺激存在的防御反应（恐惧/防御测试 电池），或潜在威胁（焦虑/防御测试电池）。 展示 威胁刺激引发逃跑、冻结、防御威胁和防御 冷冻时咬伤、风险评估和抑制 非防御行为被视为部分掠夺性刺激或场所 曾见过掠食者的地方。 因为这些测试不使用痛苦 刺激或涉及学习对与疼痛相关的刺激的反应， 它们在分析上不如传统的焦虑模型复杂，但是 提供全方位的防御行为分析双向 与施用药理学化合物相关的变化。 苯二氮卓类药物、5-HT 配体和丙咪嗪的研究表明 具有抗焦虑临床功效的药物会产生特定的效果 风险评估的变化模式和非防御性抑制 行为，在 NMDA 拮抗剂 MK-801 中也发现，但在 吗啡、东莨菪碱或阿普唑仑。 相比之下，引起恐慌的 育亨宾剂减少冻结并增强飞行和回避， 表明这些行为与目标症状之间的关系 的惊恐发作。 这项工作的另一个特点是 一致发现防御行为和防御行为中的性别差异 在这些啮齿动物模型中，对抗焦虑药物的敏感性。 拟议的计划将使用这些测试电池，并进行以下测试 抗捕食者的发声和分析可区分抗焦虑症 和镇静特性，以研究效果模式 苯二氮卓受体部分激动剂、额外的 5-HT 配体，以及 3 类具有新作用的化合物（CCK、CRF 和 NMDA 配体）， 包括其他致恐慌剂。 该计划将提供一个 对神经行为防御的药理学进行更精细的分析 以前已经可用的系统，并且将另外允许 分析与焦虑相关的防御行为中的性别影响， 以及对不同类别的抗焦虑药物的反应。