A Quantitative Approach for Detecting Anxiolytic Drug Effects in the Mouse

检测小鼠抗焦虑药物作用的定量方法

• 批准号: 7305447
• 负责人: Laurence H. Tecott
• 金额: $ 20.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-17 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7305447
• 关键词: Acute; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Anxiety Disorders; BALB/cJ Mouse; Behavior; Behavior assessment; Behavioral; Behavioral Assay; Biological Assay; Buspirone; Characteristics; Chlordiazepoxide; Chronic; Complex; Data; Data Set; Desipramine; Detection; Development; Diazepam; Exhibits; Exploratory Behavior; Fluoxetine; Genes; Genetic; Goals; Home environment; Inbred Strains Mice; Light; Measures; Methods; Monitor; Motor Activity; Mouse Strains; Mus; Mutation; Neurons; Pattern; Pentylenetetrazole; Pharmaceutical Preparations; Piperazines; Procedures; Property; Purpose; Range; Regulation; Reproducibility; Resolution; Rest; Selective Serotonin Reuptake Inhibitor; Serotonin; Serotonin Receptor 5-HT2C; Spatial Distribution; Specificity; Standards of Weights and Measures; Stimulus; System; Testing; Therapeutic; Therapeutic Agents; Tricyclic Antidepressive Agents; Validation; base; behavior measurement; environmental stressor; feeding; genetic resource; neuromechanism; novel; novel strategies; novel therapeutics; piperazine; relating to nervous system; response; restraint stress; reuptake; stressor; tool

DESCRIPTION (provided by applicant): The proliferation of mouse lines bearing mutations of neural genes presents new opportunities for inroads into the neural bases of complex behaviors, such as the regulation of anxiety. Our ability to optimally utilize mouse genetic resources for this purpose is critically dependent on the reliability and sensitivity of behavioral assays. Although standard approaches for assessing anxiety-related behavior in mice have been of substantial benefit, widely recognized limitations in the accuracy, sensitivity and reproducibility of such assays warrant initiatives for the development of novel complementary approaches. We propose to adapt a unique quantitative approach to the analysis of mouse home cage behavior to this problem. We will test the hypothesis that environmental and pharmacological manipulations that modulate anxiety will impact the coordinated expression of spontaneous behaviors exhibited by mice in their home cages. We propose that quantitative analysis of high-resolution home cage behavioral datasets can be adapted to provide a highly sensitive assessment of novel anxiety- related behavioral measures. The proposal consists of 3 Aims. In Aim 1 we will examine the sensitivity of home cage behavioral patterns to stressors, with the goal of identifying potential candidate anxiety measures. Two inbred mouse strains believed to differ in their expression of anxiety-related behaviors will be used. In Aim 2, a pharmacological validation approach will be taken to assess the extent to which these measures are appropriately modified by known anxiolytic and anxiogenic drugs. The specificity of these measures will be explored by examining their sensitivity to behaviorally active drugs not known to modulate anxiety. In Aim 3, we will determine the extent to which quantitative home cage behavioral monitoring approaches may be used to detect slow-onset anxiolytic effects produced by chronic treatment with the serotonin reuptake blocker fluoxetine and the tricyclic antidepressant desipramine. Strains of mice known to respond differently to chronic fluoxetine treatment, C57BL/6J and BALB/cJ, will be used for these studies. Limitations in behavioral assessment methods for determining anxiety levels in the mouse are hindering the development of novel therapeutic agents for anxiety disorders. Here we propose to adapt a novel quantitative behavioral monitoring method we have developed to derive and validate new markers of anxiety state.

描述（由申请人提供）：神经基因突变的小鼠线的扩散为进入复杂行为的神经碱基（例如焦虑的调节）提供了新的机会。我们最佳利用小鼠遗传资源为此目的的能力取决于行为测定的可靠性和敏感性。尽管评估小鼠中与焦虑相关行为的标准方法具有很大的好处，但这种测定法的准确性，敏感性和可重复性的限制得到了广泛认可的限制，以制定新的互补方法的制定计划。我们建议将一种独特的定量方法调整为分析小鼠家居行为的分析。我们将检验以下假设：调节焦虑的环境和药理操作将影响小鼠在其家笼中表现出的自发行为的协调表达。我们建议，可以对高分辨率房屋笼子行为数据集进行定量分析，以提供对新型焦虑相关行为度量的高度敏感评估。该提案包括3个目标。在AIM 1中，我们将检查家庭笼子行为模式对压力源的敏感性，以确定潜在的候选焦虑措施。将使用两种近交小鼠菌株在其与焦虑相关行为的表达上有所不同。在AIM 2中，将采取一种药理验证方法来评估已知的抗焦虑药和焦虑药物对这些措施进行适当修改的程度。这些措施的特异性将通过检查它们对不知道调节焦虑的行为活性药物的敏感性。在AIM 3中，我们将确定可以使用定量的家居行为监测方法来检测慢性治疗与5-羟色胺再摄取阻滞剂Fluoxetine和三环抗抑郁剂desipramine产生的缓慢发作的抗焦虑作用。这些研究将使用已知对慢性氟西汀治疗的反应不同的小鼠C57BL/6J和BALB/CJ的菌株将用于这些研究。行为评估方法确定小鼠焦虑水平的局限性正在阻碍焦虑症的新型治疗剂的发展。在这里，我们建议适应一种新型的定量行为监测方法，我们开发了旨在得出和验证焦虑状态的新标记。