Enhancement of alcohol drinking in mice depends on alterations in RNA editing of serotonin 2C receptors.
Enhancement of alcohol drinking in mice depends on alterations in RNA editing of serotonin 2C receptors.
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DOI：
10.1017/s1461145713001545
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Tanaka M
中科院分区：
文献类型：
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作者：
Watanabe Y;Yoshimoto K;Tatebe H;Kita M;Nishikura K;Kimura M;Tanaka M
血清素 2C 受体 (5-HT2CR) 是 G 蛋白偶联受体，具有多种作用，包括参与药物成瘾。 5-HT2CR 经历 mRNA 编辑，通过作用于 RNA (ADAR) 的腺苷脱氨酶将基因组编码的腺苷残基转化为肌苷。在这里，我们表明，小鼠饮酒行为的增强与伏隔核和中缝背核中 5-HT2CR mRNA 编辑的程度有关，这些区域对于奖赏和成瘾很重要。长期接触酒精蒸气后，C57BL/6J 小鼠的自愿酒精摄入量增加，但 C3H/HeJ 和 DBA/2J 小鼠的自愿酒精摄入量保持不变。在 C57BL/6J 小鼠中，两个区域的 5-HT2CR mRNA 编辑频率均显着增加，5-HT2CR、ADAR1 和 ADAR2 的表达也显着增加，但在其他品系中则没有。此外，与野生型小鼠相比，在 C57BL/6J 背景上专门表达 5-HT2CR mRNA 未编辑亚型 (INI) 的小鼠并未表现出酒精摄入量增加。我们的结果表明，5-HT2CR mRNA 编辑的改变是小鼠酒精偏好的基础。
Serotonin 2C receptors (5-HT2CR) 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-HT2CR 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-HT2CR mRNA editing frequency in both regions increased significantly in C57BL/6J mice, as did expressions of 5-HT2CR, ADAR1 and ADAR2, but not in other strains. Moreover, mice that exclusively express the unedited isoform (INI) of 5-HT2CR mRNA on a C57BL/6J background did not exhibit increased alcohol intake compared with wild-type mice. Our results indicate that alterations in 5-HT2CR mRNA editing underlie alcohol preference in mice.