Zebrafish Neuroscience Research Consortium-ZNRC and ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA.
Pharmacol Biochem Behav. 2013 Jul;108:54-60. doi: 10.1016/j.pbb.2013.04.002. Epub 2013 Apr 11.
A metabolite of the kynurenine pathway, kynurenic acid (KYNA) is an important endogenous neuromodulator and neuroprotector, that also exerts neurotropic effects following exogenous administration. In humans and animals, KYNA regulates affective and cognitive responses, acting mainly as an antagonist of glutamatergic receptors. However, the complete psychopharmacological profile of KYNA (which includes the activity of several neurotransmitter receptors) is poorly understood, and merit further studies. Aquatic models are rapidly emerging as useful tools in translational psychopharmacology research. Here, we exposed adult zebrafish (Danio rerio) to exogenous KYNA for 20 min, and assessed their behavior in the novel tank test. Exposure to KYNA (20 mg/L) in this paradigm evoked overt effects in fish, including decreased latency to enter the top half of the tank, increased number of top entries and longer top duration. In contrast, locomotor activity indices (swimming distance and velocity) were not affected by KYNA in this study. Overall, our results show KYNA has an anxiolytic-like pharmacological effect in zebrafish, and therefore strongly support the utility of zebrafish models in neurotropic drug screening, including drugs acting at central glutamatergic system. Robust phenotypic differences evoked by KYNA, revealed here using three-dimensional (3D) reconstructions of zebrafish locomotion in X, Y and time (Z) coordinates, confirm this notion, also demonstrating the value of 3D-based phenotyping approaches for high-throughput drug screening using zebrafish models.
色氨酸代谢产物犬尿氨酸（KYNA）是一种重要的内源性神经调质和神经保护剂，外源性给予也具有神经营养作用。在人类和动物中，KYNA 调节情感和认知反应，主要作为谷氨酸能受体的拮抗剂起作用。然而，KYNA 的完整精神药理学特征（包括几种神经递质受体的活性）了解甚少，值得进一步研究。水生模型作为转化精神药理学研究的有用工具正在迅速出现。在这里，我们将成年斑马鱼（Danio rerio）暴露于外源性 KYNA 20 分钟，并在新的坦克测试中评估它们的行为。在这种范式中，暴露于 KYNA（20 mg/L）会引起鱼类明显的效应，包括进入水箱上半部分的潜伏期降低、进入上半部分的次数增加和上半部分的持续时间延长。相比之下，在本研究中，运动活动指数（游泳距离和速度）不受 KYNA 的影响。总体而言，我们的结果表明 KYNA 在斑马鱼中具有抗焦虑样的药理学作用，因此强烈支持使用斑马鱼模型进行神经营养药物筛选，包括作用于中枢谷氨酸能系统的药物。KYNA 引起的明显表型差异，这里使用 X、Y 和时间（Z）坐标的斑马鱼运动的三维（3D）重建来揭示，证实了这一观点，还证明了基于 3D 的表型分析方法在使用斑马鱼模型进行高通量药物筛选中的价值。
