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本文引用的文献

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Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards.中缝背核 5-羟色胺能神经元的激活对于延迟奖励的等待是必要的。
J Neurosci. 2012 Aug 1;32(31):10451-7. doi: 10.1523/JNEUROSCI.0915-12.2012.
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Serotonin2C receptors in the nucleus accumbens are involved in enhanced alcohol-drinking behavior.伏隔核中的 5-羟色胺 2C 受体参与增强的饮酒行为。
Eur J Neurosci. 2012 Apr;35(8):1368-80. doi: 10.1111/j.1460-9568.2012.08037.x.
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Transcriptional and epigenetic mechanisms of addiction.成瘾的转录和表观遗传机制。
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Functional relevance of serotonin 2C receptor mRNA editing in antidepressant- and anxiety-like behaviors.5-羟色胺 2C 受体 mRNA 编辑在抗抑郁和焦虑样行为中的功能相关性。
Neuropharmacology. 2010 Nov;59(6):468-73. doi: 10.1016/j.neuropharm.2010.06.009. Epub 2010 Jul 17.
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Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass.血清素2C受体mRNA的编辑失调会导致能量消耗和脂肪量减少。
J Neurosci. 2008 Nov 26;28(48):12834-44. doi: 10.1523/JNEUROSCI.3896-08.2008.
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Newly identified ADAR-mediated A-to-I editing positions as a tool for ALS research.新确定的ADAR介导的A到I编辑位点作为肌萎缩侧索硬化症（ALS）研究的工具。
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RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function.血清素5HT2C受体的RNA编辑及其对细胞信号传导、药理学和脑功能的影响。
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Strain differences in alcohol-induced neurochemical plasticity: a role for accumbens glutamate in alcohol intake.酒精诱导的神经化学可塑性中的品系差异：伏隔核谷氨酸在酒精摄入中的作用。
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小鼠饮酒量的增加取决于血清素2C受体RNA编辑的改变。

Enhancement of alcohol drinking in mice depends on alterations in RNA editing of serotonin 2C receptors.

作者信息

Watanabe Yoshihisa, Yoshimoto Kanji, Tatebe Harutsugu, Kita Masakazu, Nishikura Kazuko, Kimura Minoru, Tanaka Masaki

机构信息

Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.

Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.

出版信息

Int J Neuropsychopharmacol. 2014 May;17(5):739-51. doi: 10.1017/S1461145713001545. Epub 2013 Dec 17.

DOI:10.1017/S1461145713001545
PMID:24345557
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4220740/
Abstract

Serotonin 2C receptors (5-HT(2C)R) are G-protein-coupled receptors with various actions, including involvement in drug addiction. 5-HT2CR undergoes mRNA editing, converting genomically encoded adenosine residues to inosines via adenosine deaminases acting on RNA (ADARs). Here we show that enhanced alcohol drinking behaviour in mice is associated with the degree of 5-HT(2C)R mRNA editing in the nucleus accumbens and dorsal raphe nuceus, brain regions important for reward and addiction. Following chronic alcohol vapour exposure, voluntary alcohol intake increased in C57BL/6J mice, but remained unchanged in C3H/HeJ and DBA/2J mice. 5-HT(2C)R mRNA editing frequency in both regions increased significantly in C57BL/6J mice, as did expressions of 5-HT(2C)R, ADAR1 and ADAR2, but not in other strains. Moreover, mice that exclusively express the unedited isoform (INI) of 5-HT(2C)R mRNA on a C57BL/6J background did not exhibit increased alcohol intake compared with wild-type mice. Our results indicate that alterations in 5-HT(2C)R mRNA editing underlie alcohol preference in mice.

摘要

5-羟色胺2C受体（5-HT(2C)R）是一种G蛋白偶联受体，具有多种作用，包括参与药物成瘾。5-HT2CR会进行mRNA编辑，通过作用于RNA的腺苷脱氨酶（ADARs）将基因组编码的腺苷残基转化为肌苷。在此，我们表明，小鼠中增强的饮酒行为与伏隔核和中缝背核中5-HT(2C)R mRNA的编辑程度相关，这两个脑区对奖赏和成瘾很重要。在长期暴露于酒精蒸汽后，C57BL/6J小鼠的自愿酒精摄入量增加，但C3H/HeJ和DBA/2J小鼠的摄入量保持不变。C57BL/6J小鼠这两个脑区的5-HT(2C)R mRNA编辑频率显著增加，5-HT(2C)R、ADAR1和ADAR2的表达也增加，但其他品系小鼠则不然。此外，在C57BL/6J背景下仅表达5-HT(2C)R mRNA未编辑异构体（INI）的小鼠与野生型小鼠相比，酒精摄入量并未增加。我们的结果表明，5-HT(2C)R mRNA编辑的改变是小鼠酒精偏好的基础。