关键词: 3Rs alternative model anxiety-like behavior behavioral repertoire drug discovery embryo-larval stage neurological drugs neurotransmitters

Mesh : Animals Behavior, Animal / physiology Drug Evaluation, Preclinical / methods Larva / physiology Mammals Neurotransmitter Agents Phenotype Zebrafish / genetics

来  源:   DOI:10.3390/ijms23126647

Abstract:
To discover new molecules or review the biological activity and toxicity of therapeutic substances, drug development, and research relies on robust biological systems to obtain reliable results. Phenotype-based screenings can transpose the organism\'s compensatory pathways by adopting multi-target strategies for treating complex diseases, and zebrafish emerged as an important model for biomedical research and drug screenings. Zebrafish\'s clear correlation between neuro-anatomical and physiological features and behavior is very similar to that verified in mammals, enabling the construction of reliable and relevant experimental models for neurological disorders research. Zebrafish presents highly conserved physiological pathways that are found in higher vertebrates, including mammals, along with a robust behavioral repertoire. Moreover, it is very sensitive to pharmacological/environmental manipulations, and these behavioral phenotypes are detected in both larvae and adults. These advantages align with the 3Rs concept and qualify the zebrafish as a powerful tool for drug screenings and pre-clinical trials. This review highlights important behavioral domains studied in zebrafish larvae and their neurotransmitter systems and summarizes currently used techniques to evaluate and quantify zebrafish larvae behavior in laboratory studies.
摘要:
发现新分子或审查治疗物质的生物活性和毒性,药物开发,和研究依赖于强大的生物系统来获得可靠的结果。基于表型的筛查可以通过采用多靶点策略治疗复杂疾病来转置生物体的代偿途径,斑马鱼成为生物医学研究和药物筛选的重要模型。斑马鱼的明确的神经解剖和生理特征和行为之间的相关性是非常相似的,在哺乳动物验证,能够为神经系统疾病研究构建可靠和相关的实验模型。斑马鱼表现出高度保守的生理途径,在高等脊椎动物中发现,包括哺乳动物,以及强大的行为库。此外,它对药理/环境操作非常敏感,这些行为表型在幼虫和成虫中都能检测到。这些优势与3Rs概念一致,并使斑马鱼成为药物筛选和临床前试验的强大工具。这篇综述重点介绍了在斑马鱼幼虫及其神经递质系统中研究的重要行为领域,并总结了目前在实验室研究中评估和量化斑马鱼幼虫行为的技术。
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