人类研究表明，遗传因素会导致个体易受药物依赖的影响，但很少有基因标记被确定。尽管如此，最近的证据表明，根据少数可用的遗传标记根据个人特征定制治疗可以改善治疗结果。冲动和求新是易发生药物依赖的危险因素;求新倾向预示着开始吸毒的倾向，冲动性与强迫性吸毒的进展和戒断后再次吸毒(复发)有关。后几个方面是药物成瘾的主要特征，复发是治疗的最大挑战。增加对基因对药物寻求行为的贡献的理解将有助于新疗法的发展，以改善治疗结果。在这里，我们对斑马鱼的冲动性和求新欲进行了分析，并利用这些分析对品系进行选择性繁殖，以确定导致药物成瘾的遗传机制。我们先前已经证明斑马鱼对药物滥用有一个保守的奖励反应，并开发了斑马鱼强迫性药物寻求和复发的分析方法。在这里，我们使用在啮齿类动物中使用的新对象、开放场试验和延迟奖励任务的修改，来将斑马鱼的新奇寻求和冲动与药物寻求行为联系起来。一旦研究出斑马鱼寻药预测的分析方法，我们将用它们来筛选enu诱变鱼家族的成年鱼，以建立显示改变了的寻药行为的系。 ENU-mutagenesis introduces single nucleotide variations in the genome that may alter drug seeking behaviour and act as markers for genome association studies. The existence of ENU-mutagenised zebrafish lines is an enormous resource facilitating the identification of linked alleles in zebrafish not available in other vertebrate species. In order to obtain a similar resource in rodents expensive, ethically and technically challenging mutagenesis programmes would be required. As the neurochemical pathways involved in drug seeking are evolutionarily conserved and there is a high degree of sequence and functional homology between zebrafish and mammalian genes, results found in zebrafish have translational relevance. Use of zebrafish for neurobehavioural research represents a great opportunity for reduction of the use of higher order vertebrate species thereby reducing animal suffering. The development of zebrafish lines with heightened sensitivity to drugs of abuse and establishment of suitable assays has the potential to minimise costs, both material and ethical, in drug development programmes.
