Robotics may help unravel the biological determinants of substance use disorders: studies in zebrafish

1.总结 物质使用障碍（SUD），即尽管对患者有负面影响，但仍继续使用物质。 个体（戒断症状、社会和功能障碍），构成了一个主要的社会和 经济负担。虽然许多人都有过吸毒的经历，但只有少数人会出现SUD：了解SUD的作用， 管制从使用过渡到滥用的基本机制是一项重大挑战， 生物医学科学遗传和环境因素都被认为起着至关重要的作用;然而， 他们的确切贡献仍然难以捉摸。临床前研究可以弥补这一差距，因为它们允许 剖析了几个独立变量的作用。斑马鱼作为实验动物的势头越来越猛 物种所拥有的：完全测序的基因组;代际时间短;以及对环境的快速适应性 不同的环境。尽管它们在基因x环境相互作用研究中具有潜力， 解决药物暴露后果的范例依赖于二维（2D）评分 轨迹，即使斑马鱼在3D中游泳。为了调节情绪反应，这些范例通常使用 现场刺激，这可能代表不一致的刺激，从而有利于实验偏差。最后，社会 行为通过调查群体变量的方法进行评分，但无法量化表现出的行为 一个人在一个群体中游泳。在此，我们将通过创新的机器人技术弥合这些差距- 支持的平台，再加上3D跟踪系统，可以自动调查斑马鱼的个体和社会 行为后者将允许调查如何一个人-暴露于乙醇，镇静剂，或 兴奋剂-行为孤立，或一旦引入一组未经处理的浅滩成员。技术 和方法的进步，自由传播给科学界，将使假设- 驱动的实验，旨在调查管理SUD的基本机制。这些目标将是 通过跨学科的努力实现了工程和行为神经科学的桥梁。

1. SUMMARY Substance use disorders (SUDs), the continuous use of substances in spite of negative consequences for the individual (withdrawal symptoms, social and functional impairments), constitutes a major societal and economical burden. While many individuals experience with drugs, only few develop SUDs: understanding the fundamental mechanisms regulating the transition from use to abuse constitutes a major challenge in biomedical sciences. Both genetic and environmental factors have been proposed to play a crucial role; yet, their precise contribution has remained elusive. Preclinical studies may bridge this gap as they allow for dissecting the role of several independent variables. Zebrafish are gaining momentum as a laboratory animal species as they have: a fully sequenced genome; a short intergeneration time; and a rapid adaptability to different environments. Despite their potential for gene x environment interaction studies, experimental paradigms addressing the consequences of drug exposure rest upon scoring two-dimensional (2D) trajectories, even though zebrafish swim in 3D. To modulate emotional responses, these paradigms often use live stimuli, which may represent inconsistent stimuli, thereby favoring experimental bias. Finally, social behavior is scored through methods that investigate group variables, but fail to quantify the behavior exhibited by an individual subject swimming in a group. Herein, we will bridge these gaps through an innovative robotics- enabled platform, coupled with a 3D tracking system to automatically investigate zebrafish individual and social behavior. The latter will allow for investigating how a single individual – exposed to ethanol, sedatives, or stimulants – behaves in isolation, or once introduced in a group of untreated shoal-members. Technological and methodological advances, to be freely disseminated to the scientific community, will enable hypothesis- driven experiments aimed at investigating the fundamental mechanisms governing SUD. These aims will be achieved through a multidisciplinary effort bridging engineering and behavioral neuroscience.