Animal Models of Depression

抑郁症动物模型

• 批准号: 6794879
• 负责人: JAY MICHAEL WEISS
• 金额: $ 27.75万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-11 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6794879
• 关键词: antidepressants; behavior test; behavioral /social science research tag; bipolar depression; chemotherapy; depression; disease /disorder model; drug screening /evaluation; laboratory rat; model design /development; nonhuman therapy evaluation; stress

The proposed project will examine effects of a number of drugs supplied by GlaxoSmithKline, assessing these drugs for their potential antidepressant capability. Assessment will be made primarily using two new animal models. One of these is a new screening technique for effective antidepressant treatments that appears to be more selective for detecting effective antidepressant drugs than is previously-developed screening techniques. This model uses a selectively-bred line of rats, the Swim-test Susceptible rat (or Susceptible rat), that shows heightened vulnerability to having its active behavior in a swim test reduced when it is exposed to a mild stress situation prior to the swim test. Chronic treatment with antidepressant drugs has been found to block this vulnerability; chronic treatment with other psychoactive drugs is without effect. Thus, this test appears usable to detect antidepressant drugs, and to discriminate these from other psychoactive drugs. The second model is a new rodent model of depression in which the animals show long-lasting symptoms of depression (i.e., 20-35 days duration) following a single exposure to a stressful situation. In previously-existing rodent models, depression-like symptoms have been transitory (i.e., lasted 2-4 days); thus, previous models did not allow drugs to be administered after onset of depressive symptoms so that recovery could be observed as it occurs in humans. This new model permits this to be done. The model in which long-lasting symptoms occur uses another selectively-bred rat- the Hyperactive rat. In addition to testing of drugs in these models, drugs also will be tested in a standard Porsolt swim test. Finally, additional development of animal models is proposed. In this regard, we will (a) attempt to further perfect the Hyperactive rat as a potential model for study of bipolar disorder, and (b) subject our selectively-bred rats to maternal separation as a possible means of producing improved models of affective disorders.

拟议的项目将检查葛兰素史克提供的多种药物的效果， 评估这些药物的潜在抗抑郁能力。将进行评估 主要使用两种新的动物模型。其中之一是一种新的有效筛选技术 与之前开发的筛选技术相比，抗抑郁治疗似乎在检测有效抗抑郁药物方面更具选择性。该模型使用选择性培育的大鼠品系，即游泳测试易感大鼠（或易感大鼠），当其在游泳前暴露于轻度应激情况时，其在游泳测试中的主动行为表现出高度脆弱性。测试。研究发现，长期使用抗抑郁药物治疗可以消除这种脆弱性。长期使用其他精神活性药物治疗没有效果。因此，该测试似乎可用于检测抗抑郁药物，并将其与其他精神活性药物区分开来。第二种模型是一种新的抑郁症啮齿动物模型，其中动物在单次暴露于压力环境后表现出持久的抑郁症状（即持续 20-35 天）。在先前存在的啮齿动物模型中，抑郁样症状是暂时的（即持续 2-4 天）；因此，以前的模型不允许在抑郁症状出现后服用药物，以便观察人类的恢复情况。这个新模型允许做到这一点。出现长期症状的模型使用另一种选择性繁殖的大鼠——过度活跃大鼠。除了在这些模型中测试药物外，还将在标准 Porsolt 游泳测试中对药物进行测试。最后，提出了动物模型的进一步开发。在这方面，我们将（a）尝试进一步完善多动大鼠作为双相情感障碍研究的潜在模型，以及（b）将我们选择性繁殖的大鼠进行母体分离，作为产生改进的情感障碍模型的可能手段。