Department of Psychology, University of Toronto at Mississauga, Ontario, Canada.
Genes Brain Behav. 2009 Aug;8(6):586-99. doi: 10.1111/j.1601-183X.2009.00488.x. Epub 2009 Feb 19.
The zebrafish has been in the forefront of developmental genetics for decades and has also been gaining attention in neurobehavioral genetics. It has been proposed to model alcohol-induced changes in human brain function and behavior. Here, adult zebrafish populations, AB and SF (short-fin wild type), were exposed to chronic treatment (several days in 0.00% or 0.50% alcohol v/v) and a subsequent acute treatment (1 h in 0.00%, 0.25%, 0.50% or 1.00% alcohol). Behavioral responses of zebrafish to computer-animated images, including a zebrafish shoal and a predator, were quantified using videotracking. Neurochemical changes in the dopaminergic and serotoninergic systems in the brain of the fish were measured using high-precision liquid chromatography with electrochemical detection. The results showed genetic differences in numerous aspects of alcohol-induced changes, including, for the first time, the behavioral effects of withdrawal from alcohol and neurochemical responses to alcohol. For example, withdrawal from alcohol abolished shoaling and increased dopamine and 3,4-dihydroxyphenylacetic acid in AB but not in SF fish. The findings show that, first, acute and chronic alcohol induced changes are quantifiable with automated behavioral paradigms; second, robust neurochemical changes are also detectable; and third, genetic factors influence both alcohol-induced behavioral and neurotransmitter level changes. Although the causal relationship underlying the alcohol-induced changes in behavior and neurochemistry is speculative at this point, the results suggest that zebrafish will be a useful tool for the analysis of the biological mechanisms of alcohol-induced functional changes in the adult brain.
斑马鱼在发育遗传学领域已经处于前沿地位，近年来在神经行为遗传学领域也受到关注。它被提议用于模拟酒精对人类大脑功能和行为的影响。在这里，成年斑马鱼群体 AB 和 SF（短鳍野生型）被暴露于慢性处理（在 0.00%或 0.50%酒精 v/v 中几天）和随后的急性处理（在 0.00%、0.25%、0.50%或 1.00%酒精中 1 小时）。使用视频跟踪技术对斑马鱼对计算机动画图像（包括斑马鱼鱼群和捕食者）的行为反应进行了量化。使用高精度液相色谱电化学检测测量了鱼类大脑中多巴胺能和血清素能系统的神经化学变化。结果表明，遗传差异在酒精诱导变化的许多方面都存在，包括首次观察到酒精戒断的行为效应和对酒精的神经化学反应。例如，酒精戒断会使 AB 鱼而非 SF 鱼的聚群行为消失，并增加多巴胺和 3,4-二羟基苯乙酸。研究结果表明，首先，使用自动化行为范式可以量化急性和慢性酒精诱导的变化；其次，也可以检测到强大的神经化学变化；第三，遗传因素影响酒精诱导的行为和神经递质水平变化。尽管目前在行为和神经化学变化的酒精诱导变化的因果关系仍在推测之中，但结果表明，斑马鱼将成为分析成年大脑中酒精诱导的功能变化的生物学机制的有用工具。
