Gerlai Robert, Lee Vallent, Blaser Rachel
Department of Psychology, University of Toronto @ Mississauga, 3359 Mississauga Road, Mississauga, Ontario, Canada L5L 1C6.
Pharmacol Biochem Behav. 2006 Dec;85(4):752-61. doi: 10.1016/j.pbb.2006.11.010. Epub 2006 Dec 29.
The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.g., rodents, zebrafish behavior is understudied and very few behavioral paradigms exist for mutation or drug screening purposes. Alcoholism is one of the biggest and costliest diseases whose mechanisms are not well understood. Model organisms such as the zebrafish may be utilized in this line of research. Previously, we investigated the effects of acute ethanol exposure on adult zebrafish using four behavioral paradigms and employing manual quantification methods. Here, we study the effects of chronic ethanol exposure and analyze how it modifies the effects of acute ethanol treatment. We employ a videotracking-based automated quantification method in a predator model paradigm and show that this method is capable of detecting an avoidance reaction that is ameliorated by higher doses of ethanol, a potential anxiolytic effect. Importantly, we also demonstrate that chronic, two week long, exposure to ethanol results in significant adaptation to this substance in adult zebrafish. Overall, our results suggest that zebrafish will be an appropriate subject for high throughput screening applications aimed at the analysis of the mechanisms and pharmacology of acute and chronic ethanol induced changes in the vertebrate brain.
在过去三十年里,斑马鱼一直是胚胎学和遗传学研究的热门对象。然而,最近人们对其神经生物学和行为的兴趣也有所增加。尽管如此,与其他模式生物(如啮齿动物)相比,斑马鱼的行为研究较少,用于突变或药物筛选的行为范式也非常少。酒精中毒是最大且成本最高的疾病之一,其发病机制尚未完全明了。斑马鱼等模式生物可用于这方面的研究。此前,我们使用四种行为范式并采用手动量化方法,研究了急性乙醇暴露对成年斑马鱼的影响。在此,我们研究慢性乙醇暴露的影响,并分析其如何改变急性乙醇处理的效果。我们在捕食者模型范式中采用基于视频跟踪的自动量化方法,结果表明该方法能够检测到一种回避反应,高剂量乙醇可改善这种反应,这可能是一种抗焦虑作用。重要的是,我们还证明,成年斑马鱼经两周的慢性乙醇暴露后会对该物质产生显著适应性。总体而言,我们的结果表明,斑马鱼将是高通量筛选应用的合适对象,旨在分析急性和慢性乙醇诱导的脊椎动物大脑变化的机制和药理学。