Department of Psychology, University of Toronto Mississauga, Canada.
Department of Cell and System Biology, University of Toronto, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Apr 20;83:127-136. doi: 10.1016/j.pnpbp.2018.01.012. Epub 2018 Jan 31.
The growing popularity of zebrafish in psychopharmacology and behavioral brain research is partly due to the practicality and simplicity of drug administration in this species. Several drugs may be administered to zebrafish by immersing the fish in the drug solution. Furthermore, numerous drugs developed for mammals, including humans, have been found to show a similar effect profile in the zebrafish. Thus, the zebrafish has been suggested as a potentially useful animal screening tool. Despite decades of drug development, anxiety still represents a major unmet medical need, and the search for anxiolytic compounds is continuing. The zebrafish has been proposed for high throughput screens for anxiolytic compounds, and the effects of anxiolytic compounds on the behavior of zebrafish have started to be explored. Diazepam (Valium®) is a frequently prescribed human anxiolytic, a GABA receptor agonist, has also started to be tested in zebrafish, but with occasional contradicting results. Here, we investigate the effects of diazepam in larval (6-day post-fertilization old) zebrafish in a black-white preference paradigm. We found significant white preference and thigmotaxis (edge preference) in our control fish, anxiety-like responses that habituated over time. However, unexpectedly, we observed no anxiolytic effects of diazepam on these behaviors, and only detected significant motor activity reducing effect of the drug. We discuss the complex interpretation of light/dark tests in zebrafish, and also speculate about the possibility of differential GABAergic mechanisms that diazepam affects in larval vs adult zebrafish.
斑马鱼在精神药理学和行为脑科学研究中的日益普及，部分归因于其在该物种中进行药物给药的实用性和简单性。可以通过将鱼浸入药物溶液中来向斑马鱼施用几种药物。此外，已经发现许多为哺乳动物（包括人类）开发的药物在斑马鱼中表现出相似的作用模式。因此，斑马鱼已被建议作为一种潜在有用的动物筛选工具。尽管经过数十年的药物开发，焦虑仍然是一种主要的未满足的医疗需求，并且仍在继续寻找抗焦虑化合物。已经提出了斑马鱼作为高通量抗焦虑化合物筛选工具，并且已经开始探索抗焦虑化合物对斑马鱼行为的影响。地西泮（Valium®）是一种常用的人类抗焦虑药，也是 GABA 受体激动剂，也已开始在斑马鱼中进行测试，但偶尔会得到相互矛盾的结果。在这里，我们在黑白偏好范式中研究了地西泮对 6 天大的幼鱼斑马鱼的影响。我们发现，在我们的对照鱼中，存在明显的白色偏好和触觉回避（边缘偏好），这是一种焦虑样反应，随着时间的推移会习惯。然而，出人意料的是，我们没有观察到地西泮对这些行为有抗焦虑作用，仅检测到药物对运动活性有显著的降低作用。我们讨论了在斑马鱼中对光/暗测试的复杂解释，并且还推测了地西泮在幼鱼和成年斑马鱼中影响的 GABA 能机制的差异的可能性。
