Tran Steven, Muraleetharan Arrujyan, Fulcher Niveen, Chatterjee Diptendu, Gerlai Robert
Department of Cell and Systems Biology, University of Toronto, Canada.
Department of Psychology, University of Toronto Mississauga, Canada.
Behav Brain Res. 2016 Jan 1;296:26-29. doi: 10.1016/j.bbr.2015.08.029. Epub 2015 Aug 28.
Zebrafish have become a popular animal model for behavioral neuroscience with an increasing number of studies examining the effects of pharmacological compounds targeting the brain. Exposure to MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist has been shown to increase locomotor activity in zebrafish. However, others have failed to replicate this finding as several contradicting studies report no changes in locomotor activity following exposure to similar doses. In the current study we reconcile these behavioral reports by demonstrating that zebrafish do not exhibit changes in locomotor activity during exposure to non-sedative doses of MK-801. Interestingly, zebrafish do exhibit significant increases in locomotion if pre-treated with MK-801 followed by subsequent testing in a novel environment, which suggests the effects of MK-801 are context-dependent. In addition, we examine the potential role of the dopaminergic system in mediating MK-801's locomotor stimulant effect by quantifying the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the brains of zebrafish following a 30 min exposure to 10 μM of MK-801 (the dose found to induce the largest increase in locomotor activity). Our findings indicate that the MK-801-induced increase in locomotor activity is not accompanied by changes in whole-brain levels of dopamine or DOPAC. Overall, our results suggest that MK-801's context-dependent locomotor stimulant effect may be independent of whole-brain dopaminergic activation.
斑马鱼已成为行为神经科学中一种受欢迎的动物模型，越来越多的研究在考察针对大脑的药物化合物的作用效果。已表明，暴露于MK - 801（一种非竞争性N - 甲基 - D - 天冬氨酸受体拮抗剂）会使斑马鱼的运动活性增加。然而，其他研究未能重复这一发现，因为一些相互矛盾的研究报告称，暴露于相似剂量后运动活性没有变化。在本研究中，我们通过证明斑马鱼在暴露于非镇静剂量的MK - 801期间运动活性没有变化，来调和这些行为学报告。有趣的是，如果先用MK - 801预处理斑马鱼，随后在新环境中进行测试，斑马鱼的运动确实会显著增加，这表明MK - 801的作用是依赖于环境的。此外，我们通过量化斑马鱼在暴露于10μM的MK - 801（发现能诱导最大运动活性增加的剂量）30分钟后大脑中多巴胺及其代谢物3,4 - 二羟基苯乙酸（DOPAC）的水平，来研究多巴胺能系统在介导MK - 801的运动刺激作用中的潜在作用。我们的研究结果表明，MK - 801诱导的运动活性增加并未伴随着全脑多巴胺或DOPAC水平的变化。总体而言，我们的结果表明，MK - 801依赖于环境的运动刺激作用可能独立于全脑多巴胺能激活。
