Li Fei, Lin Jia, Liu Xiuyun, Li Wenhui, Ding Yifeng, Zhang Yunjian, Zhou Shuizhen, Guo Ning, Li Qiang
Translational Medical Center for Development and Disease, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China.
Department of Neurology, Children's Hospital of Fudan University, Shanghai 201102, China.
Ann Transl Med. 2018 May;6(10):173. doi: 10.21037/atm.2018.04.25.
Behavioral changes in animals reflect functional changes in their central nervous system. Neuroactive drugs that act on different neural pathways can induce specific behavioral responses; therefore, it is possible to infer the activities of neuroactive drugs by studying the behavioral changes induced by drugs of interest in animals.
In this study, AB strain zebrafish larvae at 7 days post fertilization (dpf) were treated with different concentrations of drugs that act on different neural pathways. Changes in the swimming distances of zebrafish larvae under different illumination conditions and the differences in locomotor activities between light and dark conditions (lighting motor index) were analyzed.
Among the drugs studied, different concentrations of sulpiride had no effect on larval locomotor activity either under light or dark conditions. Progressively decreased spontaneous movements were observed in zebrafish larvae treated with increasing doses of MK-801 and valproic acid. With increasing concentrations of pentylenetetrazole and yohimbine, the spontaneous movement of larval zebrafish presented a bell-shaped response. When the illumination changed from light to dark, zebrafish larvae not treated with drugs demonstrated increased locomotor activities. However, high levels of yohimbine, pentylenetetrazole decreased the degree of change in the lighting motor index.
In conclusion, drugs that affect different neural pathways exert different influences on the locomotor activities of zebrafish larvae. This study presents an initial effort to establish a framework that correlates the drug activities and the behavioral responses of zebrafish larvae under drug treatments, which may provide a potential identification of the pathways of novel drugs with neurological activities through their behavioral influences.
动物的行为变化反映其中枢神经系统的功能变化。作用于不同神经通路的神经活性药物可诱导特定的行为反应；因此，通过研究感兴趣的药物在动物身上引起的行为变化来推断神经活性药物的活性是可能的。
在本研究中，对受精后7天（dpf）的AB品系斑马鱼幼体用作用于不同神经通路的不同浓度药物进行处理。分析了斑马鱼幼体在不同光照条件下的游泳距离变化以及明暗条件之间的运动活性差异（光照运动指数）。
在所研究的药物中，不同浓度的舒必利在明或暗条件下对幼体运动活性均无影响。用递增剂量的MK-801和丙戊酸处理的斑马鱼幼体中观察到自发运动逐渐减少。随着戊四氮和育亨宾浓度的增加，斑马鱼幼体的自发运动呈现钟形反应。当光照从明变为暗时，未用药物处理的斑马鱼幼体运动活性增加。然而，高浓度的育亨宾、戊四氮降低了光照运动指数的变化程度。
总之，影响不同神经通路的药物对斑马鱼幼体的运动活性有不同影响。本研究初步努力建立一个将药物活性与药物处理下斑马鱼幼体行为反应相关联的框架，这可能通过其行为影响为具有神经活性的新型药物的作用途径提供潜在识别方法。
