Shirahase Takahira, Watanabe Yoshihisa, Tsujimura Atsushi, Kwak Shin, Yamamoto Toshiro, Kanamura Narisato, Tanaka Masaki
Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Front Behav Neurosci. 2019 Jan 15;12:331. doi: 10.3389/fnbeh.2018.00331. eCollection 2018.
RNA editing plays critical roles in normal brain function, and alteration of its activity causes various disorders. We previously found that chronic consumption of ethanol was associated with increased levels of RNA editing of serotonin 2C receptor in the nucleus accumbens (NAc). However, it remains unknown whether RNA editing in the NAc modulates alcohol addiction through the brain reward system. To investigate the involvement of NAc RNA editing in alcohol addiction, we generated NAc-specific knockout mice of the double-stranded RNA-specific adenosine deaminase using AAV-GFP/Cre and conducted a battery of behavioral tests including anxiety- and depression-like behaviors. In addition, NAc-specific knockout mice were exposed to ethanol vapor for 20 days, followed by ethanol-drinking and conditioned place preference (CPP) tests. NAc-specific knockout mice showed a significant decrease in locomotor activity in the open field test although they did not develop anxiety- and depression-like behaviors. In addition, the enhancements of ethanol intake and ethanol preference that are usually observed after chronic ethanol vapor exposure were significantly reduced in these mice. These results suggest that ADAR2-mediated RNA editing in the NAc is involved in determination of alcohol preference after chronic alcohol consumption.
RNA编辑在正常脑功能中发挥着关键作用，其活性改变会引发多种疾病。我们之前发现，长期摄入乙醇与伏隔核（NAc）中5-羟色胺2C受体的RNA编辑水平升高有关。然而，NAc中的RNA编辑是否通过脑奖赏系统调节酒精成瘾仍不清楚。为了研究NAc RNA编辑在酒精成瘾中的作用，我们使用AAV-GFP/Cre构建了NAc特异性双链RNA特异性腺苷脱氨酶基因敲除小鼠，并进行了一系列行为测试，包括焦虑和抑郁样行为测试。此外，将NAc特异性基因敲除小鼠暴露于乙醇蒸汽中20天，随后进行乙醇饮用和条件性位置偏爱（CPP）测试。NAc特异性基因敲除小鼠在旷场试验中的自发活动显著减少，尽管它们没有出现焦虑和抑郁样行为。此外，这些小鼠在长期暴露于乙醇蒸汽后通常观察到的乙醇摄入量和乙醇偏爱增强现象显著减少。这些结果表明，NAc中ADAR2介导的RNA编辑参与了长期饮酒后酒精偏爱的决定。
