Requirement of circadian genes for cocaine sensitization in Drosophila
Requirement of circadian genes for cocaine sensitization in Drosophila
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DOI：
10.1126/science.285.5430.1066
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发表时间：
1999-08-13
期刊：
影响因子：
56.9
通讯作者：
Hirsh, J
中科院分区：
文献类型：
--
作者：
Andretic, R;Chaney, S;Hirsh, J
昼夜节律钟由一个反馈回路组成，其中时钟基因有节奏地表达，从而引起RNA和蛋白质的循环水平。迄今为止发现的五个昼夜节律基因中有四个影响果蝇对游离碱可卡因的反应，对重复可卡因暴露的敏感性，这一现象也见于人类和动物模型，并与增强的药物渴望有关，在周期，时钟，周期和双倍时间突变的果蝇中消除，但在缺乏永恒基因的果蝇中则不然。由于缺乏这些基因而不致敏的果蝇不会表现出通常在可卡因暴露后观察到的酪氨酸脱羧酶的诱导。这些发现表明这些基因在调节可卡因致敏中具有意想不到的作用，并表明它们作为酪氨酸脱羧酶的调节剂发挥作用。
The circadian clock consists of a feedback loop in which clock genes are rhythmically expressed, giving rise to cycling Levels of RNA and proteins. Four of the five circadian genes identified to date influence responsiveness to free-base cocaine in the fruit fly, Drosophila melanogaster, Sensitization to repeated cocaine exposures, a phenomenon also seen in humans and animal models and associated with enhanced drug craving, is eliminated in flies mutant for period, clock, cycle, and doubletime, but not in flies lacking the gene timeless. Flies that do not sensitize owing to lack of these genes do not show the induction of tyrosine decarboxylase normally seen after cocaine exposure. These findings indicate unexpected roles for these genes in regulating cocaine sensitization and indicate that they function as regulators of tyrosine decarboxylase.