Drosophila, a genetic model system to study cocaine-related behaviors: a review with focus on LIM-only proteins.
Drosophila, a genetic model system to study cocaine-related behaviors: a review with focus on LIM-only proteins.
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DOI：
10.1016/j.neuropharm.2008.07.023
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发表时间：
2009
影响因子：
4.7
通讯作者：
Lasek AW
中科院分区：
文献类型：
--
作者：
Heberlein U;Tsai LT;Kapfhamer D;Lasek AW
在过去的十年中，果蝇黑腹果蝇，非常容易遗传，行为和分子分析，已被引入作为一种新的模式生物，以帮助破译复杂的遗传，神经化学和神经解剖学基础的行为引起的药物滥用。在这里，我们回顾这些数据，特别关注可卡因相关的行为。可卡因的几个最具特征的特性在果蝇身上得到了再现。首先，可卡因诱导果蝇的运动行为与在哺乳动物中观察到的非常相似。第二，反复服用可卡因会诱发行为敏感化，这是一种行为可塑性，被认为是成瘾的某些方面的基础。第三，多巴胺能系统在介导可卡因效应中的关键作用已通过药理学和遗传学方法得到证实。最后，也是最重要的一点是，由于实验室中可以对果蝇进行简单和规模化的操作，无偏见的遗传筛选是可行的，它已经确定了几个新的基因和途径，这些基因和途径在可卡因行为中的作用是没有预料到的。这些基因和途径中的许多已经在药物成瘾的哺乳动物模型中得到验证。我们专注于在可卡因诱导的行为中的作用LIM唯一的蛋白质在这方面的审查。
In the last decade, the fruit fly Drosophila melanogaster, highly accessible to genetic, behavioral and molecular analyses, has been introduced as a novel model organism to help decipher the complex genetic, neurochemical, and neuroanatomical underpinnings of behaviors induced by drugs of abuse. Here we review these data, focusing specifically on cocaine-related behaviors. Several of cocaine's most characteristic properties have been recapitulated in Drosophila. First, cocaine induces motor behaviors in flies that are remarkably similar to those observed in mammals. Second, repeated cocaine administration induces behavioral sensitization a form of behavioral plasticity believed to underlie certain aspects of addiction. Third, a key role for dopaminergic systems in mediating cocaine's effects has been demonstrated through both pharmacological and genetic methods. Finally, and most importantly, unbiased genetic screens, feasible because of the simplicity and scale with which flies can be manipulated in the laboratory, have identified several novel genes and pathways whose role in cocaine behaviors had not been anticipated. Many of these genes and pathways have been validated in mammalian models of drug addiction. We focus in this review on the role of LIM-only proteins in cocaine-induced behaviors.
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