Antipsychotics produce locomotor impairment in larval zebrafish
Antipsychotics produce locomotor impairment in larval zebrafish
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DOI：
10.1016/j.ntt.2006.01.013
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发表时间：
2006-03-01
影响因子：
2.9
通讯作者：
Guo, S
中科院分区：
文献类型：
--
作者：
Giacomini, NJ;Rose, B;Guo, S
斑马鱼是研究发育过程的理想模式动物。它还具有理解行为和相关行为障碍的遗传基础的巨大潜力。尽管有这样的潜力，他们在行为研究中的使用是大大不足的探索。众所周知，用于治疗精神疾病的多种类型的药物产生锥体外系（EPS）作用并随之导致人类运动障碍。这些药物引起的运动障碍的潜在分子原因知之甚少。在这里，我们报告说，斑马鱼治疗抗精神病药物氟奋乃静和氟哌啶醇（这两种药物都可以诱导严重的EPS在人类）发展运动缺陷。相比之下，另一种抗精神病药物奥氮平在人类中产生轻度至少量EPS，导致斑马鱼出现最小的运动缺陷。这些结果建立了一个快速测定系统，其中的EPS诱导剂的影响可以进行评估。因此，未来在斑马鱼中的遗传筛选将确定阐明人类药物诱导的运动障碍的基因和途径，并提供对运动活动的大脑控制的见解。未来在斑马鱼中进行的化学筛选可能会作为某些药物的EPS效应的临床前测试，以及用于研究对抗EPS效应的药物的测试。(c)2006年爱思唯尔公司All rights reserved.
Zebrafish has been a favored vertebrate genetic model organism for studying developmental processes. It also holds a great potential for understanding the genetic basis of behavior and associated behavioral disorders. Despite such potential, their use in the study of behavior is greatly under-explored. It is well known that Multiple classes of drugs used to treat psychiatric diseases produce extrapyramidal side (EPS) effects and consequent movement disorders in humans. The underlying molecular causes of these drug-induced movement disorders are poorly understood. Here we report that zebrafish treated with the antipsychotics fluphenazine and haloperidol (both of which can induce severe EPS in humans) develop movement defects. In contrast, another antipsychotic olanzapine, which produces mild to little EPS in humans, leads to minimal movement defects in zebrafish. These results establish a rapid assay system in which the effects of EPS-inducing agents can be assessed. Thus, future genetic screening in zebrafish shall identify genes and pathways that elucidate drug-induced movement disorder in human as well as provide insights into the brain control of locomotor activity. Future chemical screening in zebrafish may act as a preclinical test for the EPS effect of certain drugs, as well as a test used to researching drugs made to counteract the effects of EPS. (c) 2006 Elsevier Inc. All rights reserved.