The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

中文翻译：

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斑马鱼模型对NPS进行法医毒理学筛查的潜力：APINAC和甲硫基丙胺对斑马鱼幼虫和小鼠行为的影响的比较研究。

所谓的新型精神活性物质（NPS）的扩散增加，以及它们在结构和想像上的连续变化，导致需要一种快速筛选方法，以便在它们出现在市场后尽早发现其生物学效应。法医病理学和毒理学都非常重视这个问题，因此，临床前研究对于难以解释中毒的临床和尸检病例至关重要。斑马鱼是一种高通量的合适模型，可以快速假设新型分子的潜在厌恶或有益作用。在本研究中，我们在斑马鱼幼虫（ZL）和成年小鼠上测量并比较了对两种新型神经活​​性药物，即APINAC（一种新的大麻素药物）和甲硫丙胺（MPA）（一种甲基苯丙胺类化合物）的行为反应。通过使用创新的统计方法（通用加性模型），发现两种物种的两种药物均会损害自发运动能力：破坏程度以剂量依赖性和时间依赖性方式变化。感觉运动功能也发生了改变：i）用APINAC治疗的小鼠的视觉对象反应降低，而暴露于MPA后则没有。ii）在小鼠中用两种NPS治疗后视觉放置反应均降低。此外，在ZL中检测到的视觉运动反应显示出在用APINAC处理后在明暗过渡期间的减弱。仅在暗光过渡时，在MPA暴露组中发现了相同的模式，而在从明暗过渡时，个体显示出增强的反应。结论，