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The hangover gene defines a stress pathway required for ethanol tolerance development

机译：宿醉基因定义了乙醇耐受性发展所需的应激途径

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Repeated alcohol consumption leads to the development of tolerance, simply defined as an acquired resistance to the physiological and behavioural effects of the drug. This tolerance allows increased alcohol consumption, which over time leads to physical dependence and possibly addiction(1-3). Previous studies have shown that Drosophila develop ethanol tolerance, with kinetics of acquisition and dissipation that mimic those seen in mammals. This tolerance requires the catecholamine octopamine, the functional analogue of mammalian noradrenaline(4). Here we describe a new gene, hangover, which is required for normal development of ethanol tolerance. hangover flies are also defective in responses to environmental stressors, such as heat and the free-radical-generating agent paraquat. Using genetic epistasis tests, we show that ethanol tolerance in Drosophila relies on two distinct molecular pathways: a cellular stress pathway defined by hangover, and a parallel pathway requiring octopamine. hangover encodes a large nuclear zinc-finger protein, suggesting a role in nucleic acid binding. There is growing recognition that stress, at both the cellular and systemic levels, contributes to drug- and addiction-related behaviours in mammals. Our studies suggest that this role may be conserved across evolution.
机译：反复饮酒会导致耐受性的发展，简单地定义为对药物的生理和行为影响的获得性耐药。这种耐受性允许增加饮酒量，随着时间的流逝会导致身体依赖性和成瘾性（1-3）。先前的研究表明，果蝇具有对乙醇的耐受性，其获取和消散的动力学类似于在哺乳动物中所见到的。这种耐受性需要儿茶酚胺章鱼胺，它是哺乳动物去甲肾上腺素的功能类似物（4）。在这里，我们描述了一个新的基因，宿醉，这是乙醇耐受性正常发育所必需的。宿醉蝇对环境压力（例如热量和自由基产生剂百草枯）的响应也有缺陷。使用遗传上位性测试，我们显示果蝇中的乙醇耐受性依赖于两个不同的分子途径：由宿醉定义的细胞应激途径和需要章鱼胺的平行途径。宿醉编码大的核锌指蛋白，提示在核酸结合中起作用。越来越多的人意识到，在细胞和系统水平上的压力都会导致哺乳动物的药物和成瘾相关行为。我们的研究表明，这种作用在整个进化过程中可能是保守的。

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