Department of Pharmacology and Neuroscience Program, Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA; Zebrafish Neuroscience Research Consortium (ZNRC), Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Department of Pharmacology and Neuroscience Program, Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Behav Brain Res. 2013 Jan 1;236(1):258-269. doi: 10.1016/j.bbr.2012.08.041. Epub 2012 Sep 4.
An indole alkaloid, ibogaine is the principal psychoactive component of the iboga plant, used by indigenous peoples in West Africa for centuries. Modulating multiple neurotransmitter systems, the drug is a potent hallucinogen in humans, although its psychotropic effects remain poorly understood. Expanding the range of model species is an important strategy for translational neuroscience research. Here we exposed adult zebrafish (Danio rerio) to 10 and 20mg/L of ibogaine, testing them in the novel tank, light-dark box, open field, mirror stimulation, social preference and shoaling tests. In the novel tank test, the zebrafish natural diving response (geotaxis) was reversed by ibogaine, inducing initial top swimming followed by bottom dwelling. Ibogaine also attenuated the innate preference for dark environments (scototaxis) in the light-dark box test. While it did not exert overt locomotor or thigmotaxic responses in the open field test, the drug altered spatiotemporal exploration of novel environment, inducing clear preference of some areas over others. Ibogaine also promoted 'mirror' exploration in the mirror stimulation test, disrupted group cohesion in the shoaling test, and evoked strong coloration responses due to melanophore aggregation, but did not alter brain c-fos expression or whole-body cortisol levels. Overall, our results support the complex pharmacological profile of ibogaine and its high sensitivity in zebrafish models, dose-dependently affecting multiple behavioral domains. While future investigations in zebrafish may help elucidate the mechanisms underlying these unique behavioral effects, our study strongly supports the developing utility of aquatic models in hallucinogenic drug research. High sensitivity of three-dimensional phenotyping approaches applied here to behavioral effects of ibogaine in zebrafish provides further evidence of how 3D reconstructions of zebrafish swimming paths may be useful for high-throughput pharmacological screening.
一种吲哚生物碱，伊博加因是伊博加因植物的主要精神活性成分，几个世纪以来，非洲西部的土著人民一直在使用它。这种药物调节多种神经递质系统，在人类中是一种有效的致幻剂，尽管其精神作用仍知之甚少。扩大模型物种的范围是转化神经科学研究的重要策略。在这里，我们将成年斑马鱼（Danio rerio）暴露于 10 和 20mg/L 的伊博加因中，在新水箱、明暗箱、开阔场、镜像刺激、社会偏好和群体测试中对其进行测试。在新水箱测试中，伊博加因逆转了斑马鱼的自然潜水反应（趋地性），导致最初的顶泳，然后是底栖。伊博加因还减弱了在明暗箱测试中对黑暗环境的先天偏好（避光性）。虽然它在开阔场测试中没有表现出明显的运动或触觉反应，但该药物改变了对新环境的时空探索，明显偏好某些区域而不是其他区域。伊博加因还在镜像刺激测试中促进了“镜像”探索，在群体测试中破坏了群体凝聚力，并由于黑色素聚集引起强烈的着色反应，但没有改变大脑 c-fos 表达或全身皮质醇水平。总的来说，我们的结果支持伊博加因的复杂药理学特征及其在斑马鱼模型中的高敏感性，剂量依赖性地影响多个行为领域。虽然在斑马鱼中的未来研究可能有助于阐明这些独特行为效应的机制，但我们的研究强烈支持水生模型在致幻药物研究中的发展实用性。这里应用的三维表型方法对伊博加因在斑马鱼中的行为效应的高灵敏度提供了进一步的证据，表明如何重建斑马鱼游泳路径的 3D 结构可能有助于高通量药物筛选。
