Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.
Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.
复制标题
DOI：
10.1038/nchembio.2097
复制
发表时间：
2016-07
影响因子：
14.8
通讯作者：
Kokel D
中科院分区：
文献类型：
--
作者：
Bruni G;Rennekamp AJ;Velenich A;McCarroll M;Gendelev L;Fertsch E;Taylor J;Lakhani P;Lensen D;Evron T;Lorello PJ;Huang XP;Kolczewski S;Carey G;Caldarone BJ;Prinssen E;Roth BL;Keiser MJ;Peterson RT;Kokel D
许多精神药物作用于多个靶点，因此需要涵盖广泛靶点的筛查分析。有了足够丰富的表型和大量的化合物样本，应该可以仅根据化合物的行为特征来识别具有所需作用机制的化合物。虽然斑马鱼(Danio Rerio)的行为已经被用来快速鉴定神经活性化合物，但目前还不清楚到底需要什么样的行为分析来鉴定抗精神病药物等多靶点化合物。在这里，我们开发了一组斑马鱼幼体的行为分析，以确定行为特征是否能提供足够的表型分辨率来识别和分类精神药物。使用抗精神病药物氟哌啶醇作为测试案例，我们发现氟哌啶醇处理的动物的行为特征可以用来识别具有期望的抗精神病药样活性和多靶点作用机制的先前未确定的化合物。
Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping, and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action based on their behavioral profiles alone. Although zebrafish (Danio rerio) behaviors have been used to rapidly identify neuroactive compounds, it remains unclear exactly what kind of behavioral assays might be necessary to identify multi-target compounds such as antipsychotics. Here, we developed a battery of behavioral assays in larval zebrafish to determine if behavioral profiles could provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated animals could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multi-target mechanisms of action.