Zebrafish provide a valuable emerging complementary model for neurobehavioral research. They offer a powerful way to screen for the potential therapeutic effects of neuroactive drugs. A variety of behavioral tests for zebrafish have been developed and validated for assessing neurobehavioral function. The novel tank diving test is a straightforward, reproducible way of measuring anxiety-like behavior in zebrafish. When introduced into a novel tank, zebrafish normally dive to the bottom of the tank and then gradually explore the higher levels of the water column as time progresses. Buspirone is an effective anxiolytic drug in humans, which has been found, with acute administration, to reduce this anxiety-like response in zebrafish. The current study used the zebrafish model to evaluate the potential anxiolytic effects of alkaloids, commonly found in Solanaceae plants, with known neuropharmacology relevant to mood regulation. In line with previous findings, acute treatment with anxiolytic positive controls buspirone and the plant alkaloid nicotine reduced the anxiety-like diving response in the zebrafish novel tank diving test. Further, both buspirone and nicotine continued to produce anxiolytic-like effects in zebrafish after 5 days of exposure. In the same treatment paradigm, the effects of five other alkaloids—cotinine, anatabine, anabasine, harmane, and norharmane—were investigated. Cotinine, the major metabolite of nicotine, also caused anxiolytic-like effects, albeit at a dose higher than the effective dose of nicotine. Nicotine's anxiolytic-like effect was not shared by the other nicotinic alkaloids, anabasine and anatabine, or by the naturally present monoamine oxidase inhibitors harmane and norharmane. We conclude that nicotine uniquely induces anxiolytic-like effects after acute and subchronic treatment in zebrafish. The zebrafish model with the novel tank diving test could be a useful complement to rodent models for screening candidate compounds for anxiolytic effects in nonclinical studies.

斑马鱼为神经行为研究提供了一个有价值的新兴补充模型。它们为筛选神经活性药物的潜在治疗效果提供了一种强有力的方法。已经开发和验证了多种斑马鱼行为测试，用于评估神经行为功能。新颖的坦克潜水测试是一种直接、可重复的测量斑马鱼焦虑样行为的方法。当被引入一个新的水箱时，斑马鱼通常会潜入水箱底部，然后随着时间的推移逐渐探索水柱的更高水平。丁螺环酮是一种有效的人类抗焦虑药物，已发现急性给药可减少斑马鱼的这种焦虑样反应。目前的研究使用斑马鱼模型来评估生物碱的潜在抗焦虑作用，常见于茄科植物中，具有与情绪调节相关的已知神经药理学。与先前的研究结果一致，抗焦虑阳性对照丁螺环酮和植物生物碱尼古丁的急性治疗降低了斑马鱼新型坦克潜水试验中的焦虑样潜水反应。此外，丁螺环酮和尼古丁在暴露 5 天后继续在斑马鱼中产生抗焦虑样作用。在相同的治疗范例中，研究了其他五种生物碱——可替宁、新烟草碱、新竹碱、哈曼和去甲哈曼——的作用。尼古丁的主要代谢物可替宁也引起抗焦虑样作用，尽管其剂量高于尼古丁的有效剂量。尼古丁的抗焦虑作用是其他烟碱类生物碱、新竹碱和新烟草碱所不具备的，或通过天然存在的单胺氧化酶抑制剂harmane和norharmane。我们得出结论，尼古丁在斑马鱼急性和亚慢性治疗后独特地诱导抗焦虑样作用。具有新型坦克潜水试验的斑马鱼模型可能是啮齿动物模型的有用补充，用于在非临床研究中筛选候选化合物的抗焦虑作用。