Behavioral screening for cocaine sensitivity in mutagenized zebrafish
Behavioral screening for cocaine sensitivity in mutagenized zebrafish
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DOI：
10.1073/pnas.191380698
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Dowling, JE
中科院分区：
文献类型：
--
作者：
Darland, T;Dowling, JE
利用正向遗传操作来延长参与这一复杂过程的候选基因的名单，可以极大地帮助理解成瘾的分子基础。在这里，我们报告说，斑马鱼表现出可卡因诱导的条件性位置偏爱。在一个试点筛选的18个F-2代家庭的诱变鱼，我们发现三个异常低的反应可卡因。这种行为是由F-3代遗传的，表明这种异常是由于单个基因的显性突变。在测量视觉暗适应和学习的二级行为屏幕中的性能概况表明，这些缺陷是影响视网膜和大脑中多巴胺能信号的不同基因突变的结果。
Understanding the molecular basis of addiction could be greatly aided by using forward genetic manipulation to lengthen the list of candidate genes involved in this complex process. Here, we report that zebrafish exhibit cocaine-induced conditioned place preference. In a pilot screen of 18 F-2 generation families of mutagenized fish, we found three with abnormally low responses to cocaine. This behavior was inherited by the F-3 generation in a manner that suggests the abnormalities were because of dominant mutations in single genes. Performance profiles in secondary behavioral screens measuring visual dark-adaptation and learning suggest that the defects were the result of mutations in distinct genes that affect dopaminergic signaling in the retina and brain.