School of Pharmacy and School of Life Sciences, Southwest University, Chongqing, China.
Military Medical Academy, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia.
Neuroscience. 2019 Apr 15;404:218-232. doi: 10.1016/j.neuroscience.2019.01.045. Epub 2019 Jan 31.
Despite the high prevalence of medicinal use and abuse of opioids, their neurobiology and mechanisms of action are not fully understood. Experimental (animal) models are critical for improving our understanding of opioid effects in vivo. As zebrafish (Danio rerio) are increasingly utilized as a powerful model organism in neuroscience research, mounting evidence suggests these fish as a useful tool to study opioid neurobiology. Here, we discuss the zebrafish opioid system with specific focus on opioid gene expression, existing genetic models, as well as its pharmacological and developmental regulation. As many human brain diseases involve pain and aberrant reward, we also summarize zebrafish models relevant to opioid regulation of pain and addiction, including evidence of functional interplay between the opioid system and central dopaminergic and other neurotransmitter mechanisms. Additionally, we critically evaluate the limitations of zebrafish models for translational opioid research and emphasize their developing utility for improving our understanding of evolutionarily conserved mechanisms of pain-related, addictive, affective and other behaviors, as well as for fostering opioid-related drug discovery.
尽管阿片类药物的使用和滥用非常普遍，但它们的神经生物学和作用机制仍不完全清楚。实验（动物）模型对于提高我们对阿片类药物体内作用的理解至关重要。由于斑马鱼（Danio rerio）越来越多地被用作神经科学研究中的强大模式生物，越来越多的证据表明这些鱼类是研究阿片类神经生物学的有用工具。在这里，我们讨论了斑马鱼的阿片系统，特别关注阿片基因表达、现有的遗传模型，以及其药理学和发育调控。由于许多人类脑部疾病都涉及疼痛和异常的奖励，我们还总结了与阿片类药物调节疼痛和成瘾相关的斑马鱼模型，包括阿片系统与中枢多巴胺能和其他神经递质机制之间功能相互作用的证据。此外，我们还批判性地评估了斑马鱼模型在转化阿片类药物研究中的局限性，并强调了它们在提高我们对与疼痛相关的、成瘾性的、情感的和其他行为的进化保守机制的理解，以及促进与阿片类药物相关的药物发现方面的发展潜力。
