Department of Psychology, University of Toronto Mississauga, Canada.
Department of Cell & System Biology, University of Toronto, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20;111:110143. doi: 10.1016/j.pnpbp.2020.110143. Epub 2020 Oct 20.
Alcoholism and alcohol abuse represent a significant medical and societal problem, and have been thoroughly investigated in humans as well as using animal models. A less well understood aspect of alcohol related disorders is the possible effect of this drug on offspring whose parents were exposed prior to conception. The zebrafish has been successfully employed in alcohol research, however, the effect of exposing the parents to alcohol before fertilization of the eggs on offspring has not been demonstrated in this species. In this proof of concept study, we attempt to address this hiatus. We exposed both adult male and female zebrafish to 0.0% (control) or 0.5% (vol/vol) alcohol chronically for 7 days, subsequently bred the fish within their respective treatment group, collected the fertilized eggs, allowed them to develop, and tested the behavior of free-swimming offspring at their age of 7-9 days post-fertilization. We conducted the analysis in two genetically distinct quasi-inbred strains of zebrafish, AB and TL. Although gross morphology and general activity of the fish appeared unaffected, we found significant behavioral alterations in offspring of alcohol exposed parents compared to offspring of control parents in both strains. These alterations included robustly increased duration and reduced frequency of immobility, increased turn angle, and increased intra-individual variance of turn angle in offspring of alcohol exposed parents in both strains. The mechanisms underlying these behavioral effects or whether the effects are due to exposure of the father, the mother, or both to alcohol are unknown. Nevertheless, our results now set the stage for future studies with zebrafish that will address these questions.
酗酒和酒精滥用是一个重大的医学和社会问题，已经在人类和动物模型中进行了深入研究。与酒精相关的疾病的一个不太为人理解的方面是，这种药物可能对父母在受孕前接触过酒精的后代产生影响。斑马鱼已成功应用于酒精研究，但在这种物种中，尚未证明在受精前让父母接触酒精对后代的影响。在这项概念验证研究中，我们试图解决这一空白。我们将成年雄性和雌性斑马鱼分别暴露于 0.0%（对照）或 0.5%（体积/体积）的酒精中慢性暴露 7 天，随后在各自的处理组中繁殖鱼类，收集受精卵，让它们发育，并在受精后 7-9 天测试自由游动的后代的行为。我们在两种遗传上不同的准近交系斑马鱼 AB 和 TL 中进行了分析。尽管鱼的大体形态和一般活动似乎没有受到影响，但我们发现，与对照组的后代相比，暴露于酒精的父母的后代在两种品系中都表现出明显的行为改变。这些改变包括：暴露于酒精的父母的后代的静止时间显著增加，静止频率显著降低，转弯角度增加，个体内转弯角度的方差增加。这些行为效应的机制，或者这些效应是否是由于父亲、母亲或两者都暴露于酒精引起的，尚不清楚。然而，我们的结果现在为未来用斑马鱼进行的研究奠定了基础，这些研究将解决这些问题。
