University of California, San Francisco, CA 94143-2822, USA.
Curr Biol. 2009 Dec 29;19(24):2126-32. doi: 10.1016/j.cub.2009.10.070. Epub 2009 Dec 10.
Alcohol addiction is a common affliction with a strong genetic component [1]. Although mammalian studies have provided significant insight into the molecular mechanisms underlying ethanol consumption [2], other organisms such as Drosophila melanogaster are better suited for unbiased, forward genetic approaches to identify novel genes. Behavioral responses to ethanol, such as hyperactivity, sedation, and tolerance, are conserved between flies and mammals [3, 4], as are the underlying molecular pathways [5-9]. However, few studies have investigated ethanol self-administration in flies [10]. Here we characterize ethanol consumption and preference in Drosophila. Flies prefer to consume ethanol-containing food over regular food, and this preference increases over time. Flies are attracted to the smell of ethanol, which partially mediates ethanol preference, but are averse to its taste. Preference for consuming ethanol is not entirely explained by attraction to either its sensory or caloric properties. We demonstrate that flies can exhibit features of alcohol addiction. First, flies self-administer ethanol to pharmacologically relevant concentrations. Second, flies will overcome an aversive stimulus in order to consume ethanol. Third, flies rapidly return to high levels of ethanol consumption after a period of imposed abstinence. Thus, ethanol preference in Drosophila provides a new model for studying aspects of addiction.
酒精成瘾是一种常见的疾病,具有很强的遗传成分[1]。尽管哺乳动物研究为乙醇消费的分子机制提供了重要的见解[2],但其他生物体,如黑腹果蝇,更适合用于无偏正向遗传方法来识别新基因。对乙醇的行为反应,如兴奋、镇静和耐受,在果蝇和哺乳动物之间是保守的[3,4],其潜在的分子途径也是如此[5-9]。然而,很少有研究调查过果蝇中的乙醇自我给药[10]。在这里,我们描述了果蝇对乙醇的消耗和偏好。果蝇更喜欢含有乙醇的食物而不是普通食物,而且这种偏好会随着时间的推移而增加。果蝇对乙醇的气味有吸引力,这部分介导了乙醇的偏好,但对其味道有反感。对乙醇的偏好不能完全用其感官或热量特性来解释。我们证明果蝇可以表现出酒精成瘾的特征。首先,果蝇会自行摄取具有药理相关性的乙醇浓度。其次,果蝇会为了摄取乙醇而克服厌恶刺激。第三,在一段时间的强制禁欲后,果蝇会迅速恢复到高乙醇消耗水平。因此,果蝇对乙醇的偏好为研究成瘾的某些方面提供了一个新的模型。