Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box #104790, Durham, NC 27710, USA.
Rev Neurosci. 2011;22(1):75-84. doi: 10.1515/RNS.2011.009.
Zebrafish can provide a valuable animal model to screen potential cognitive enhancing and anxiolytic drugs. They are economical and can provide a relatively quick indication of possible functional efficacy. In as much as they have a complex nervous system and elaborate behavioral repertoire, zebrafish can provide a good intermediate model between in vitro receptor and cell-based assays and classic mammalian models for drug screening. In addition, the variety of molecular tools available in zebrafish makes them outstanding models for helping to determine the neuromolecular mechanisms for psychoactive drugs. However, to use zebrafish as a translational model we must have validated, sensitive and efficient behavioral tests. In a series of studies, our lab has developed tests of cognitive function and stress response, which are sensitive to drug effects in a similar manner as rodent models and humans for cognitive enhancement and alleviating stress response. In particular, the three-chamber task for learning and memory was shown to be sensitive to the cognitive enhancing effects of nicotine and has been useful in helping to determine neural mechanisms crucial for nicotinic-induced cognitive enhancement. The novel tank diving test was shown to be a valid and efficient test of stress response. It is sensitive to the reduction in stress-related behaviors due to the amxiolytic drugs diazepam and buspirone but not chlordiazepoxide. Nicotine also causes stress alleviating effects which can be interpreted as anxiolytic effects. Zebrafish models of behavioral pharmacology can be useful to efficiently screen test compounds for drug development and can be useful in helping to determine the mechanisms crucial for new therapeutic treatments of neurobehavioral impairments.
斑马鱼可以提供有价值的动物模型，用于筛选潜在的认知增强和抗焦虑药物。它们经济实惠，能够相对快速地显示出可能的功能效果。由于它们具有复杂的神经系统和精细的行为谱，斑马鱼可以作为体外受体和基于细胞的测定与经典的哺乳动物药物筛选模型之间的良好中间模型。此外，斑马鱼中可用的各种分子工具使它们成为确定精神药物神经分子机制的杰出模型。然而，要将斑马鱼用作转化模型，我们必须具有经过验证、敏感和有效的行为测试。在一系列研究中，我们的实验室开发了认知功能和应激反应测试，这些测试对药物的作用敏感，与啮齿动物模型和人类的认知增强和缓解应激反应相似。特别是，三箱学习和记忆任务被证明对尼古丁的认知增强作用敏感，并有助于确定尼古丁诱导的认知增强的关键神经机制。新的坦克潜水测试被证明是一种有效的应激反应测试。它对由于抗焦虑药物地西泮和丁螺环酮而导致的应激相关行为减少敏感，但对氯氮卓不敏感。尼古丁也会引起减轻压力的作用，可以解释为抗焦虑作用。行为药理学斑马鱼模型可用于有效筛选药物开发的测试化合物，并有助于确定新的神经行为障碍治疗方法的关键机制。
