Fernandes Yohaan, Rampersad Mindy, Gerlai Robert
Department of Psychology (Mr Fernandes, Ms Rampersad, and Dr Gerlai), and Department of Cell and System Biology (Dr Gerlai), University of Toronto, Mississauga, Canada.
Int J Neuropsychopharmacol. 2015 Jan 7;18(6):pyu089. doi: 10.1093/ijnp/pyu089.
The zebrafish is a powerful neurobehavioral genetics tool with which complex human brain disorders including alcohol abuse and fetal alcohol spectrum disorders may be modeled and investigated. Zebrafish innately form social groups called shoals. Previously, it has been demonstrated that a single bath exposure (24 hours postfertilization) to low doses of alcohol (0, 0.25, 0.50, 0.75, and 1% vol/vol) for a short duration (2 hours) leads to impaired group forming, or shoaling, in adult zebrafish.
In the current study, we immersed zebrafish eggs in a low concentration of alcohol (0.5% or 1% vol/vol) for 2 hours at 24 hours postfertilization and let the fish grow and reach adulthood. In addition to quantifying the behavioral response of the adult fish to an animated shoal, we also measured the amount of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid from whole brain extracts of these fish using high-pressure liquid chromatograph.
Here we confirm that embryonic alcohol exposure makes adult zebrafish increase their distance from the shoal stimulus in a dose-dependent manner. We also show that the shoal stimulus increases the amount of dopamine and 3,4-dihydroxyphenylacetic acid in the brain of control zebrafish but not in fish previously exposed to alcohol during their embryonic development.
We speculate that one of the mechanisms that may explain the embryonic alcohol-induced impaired shoaling response in zebrafish is dysfunction of reward mechanisms subserved by the dopaminergic system.
斑马鱼是一种强大的神经行为遗传学工具,借助它可以对包括酒精滥用和胎儿酒精谱系障碍在内的复杂人类脑部疾病进行建模和研究。斑马鱼天生会形成称为鱼群的社会群体。此前已证明,在受精后24小时对成年斑马鱼进行短时间(2小时)的低剂量酒精(0、0.25、0.50、0.75和1%体积/体积)单次浸浴暴露会导致其群体形成或聚群行为受损。
在本研究中,我们在受精后24小时将斑马鱼卵浸入低浓度酒精(0.5%或1%体积/体积)中2小时,然后让鱼生长至成年。除了量化成年鱼对动画鱼群的行为反应外,我们还使用高压液相色谱法测量了这些鱼全脑提取物中的多巴胺及其代谢物3,4 - 二羟基苯乙酸的含量。
在此我们证实,胚胎期酒精暴露会使成年斑马鱼以剂量依赖的方式增加其与鱼群刺激的距离。我们还表明,鱼群刺激会增加对照斑马鱼大脑中的多巴胺和3,4 - 二羟基苯乙酸含量,但在胚胎发育期间曾暴露于酒精的鱼中则不会。
我们推测,可能解释胚胎期酒精诱导的斑马鱼聚群反应受损的机制之一是多巴胺能系统所支持的奖赏机制功能障碍。