Deletion of GIRK2 subunit containing GIRK channels of neurons expressing dopamine transporter decrease immobility time on forced swimming in mice
Deletion of GIRK2 subunit containing GIRK channels of neurons expressing dopamine transporter decrease immobility time on forced swimming in mice
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DOI：
10.1016/j.neulet.2017.11.028
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发表时间：
2018-02
影响因子：
2.5
通讯作者：
Ikutaro Honda;K. Araki;Sokichi Honda;F. Soeda;M. Shin;S. Misumi;K. Yamamura;K. Takahama
中科院分区：
文献类型：
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作者：
Ikutaro Honda;K. Araki;Sokichi Honda;F. Soeda;M. Shin;S. Misumi;K. Yamamura;K. Takahama
我们先前报道对G蛋白偶联内向整流钾(GIRK)通道具有抑制作用的非麻醉性镇咳药在正常和促肾上腺皮质激素(ACTH)处理的大鼠强迫游泳试验中具有抗抑郁作用。此外，替替匹定等镇咳药的抗抑郁药样作用可被多巴胺D1受体拮抗剂阻断，对多巴胺神经元GIRK通道的抑制作用可能参与了替替匹定的抗抑郁药样作用。在这项研究中，我们产生了带有Girk2/Kcnj6条件缺失的GIRK2DATKO小鼠，并评估了这些小鼠的抑郁相关行为。Cre/loxP系统用于选择性地删除表达多巴胺转运蛋白的神经元中含有GIRK通道的GIRK2亚单位。首先，组织化学和电生理学证实腹侧被盖区(VTA)神经元表达多巴胺转运体的GIRK2亚单位缺失。在小鼠的强迫游泳实验中，观察到不动时间显著缩短。在野外测试时，与GIRK2氟化小鼠相比，小鼠的运动活动没有改变。这些结果提示，替替匹定等镇咳药的抗抑郁作用可能部分是通过抑制多巴胺神经元上的GIRK通道而实现的。
We previously reported that non-narcotic antitussives possessing inhibitory actions on G protein-coupled inwardly rectifying potassium (GIRK) channels have antidepressant-like effects in the forced swimming test in normal and adrenocoticotropic hormone (ACTH) treated rats. Furthermore, the antidepressant-like effects of the antitussives such as tipepidine were blocked by dopamine D1receptor antagonist, and inhibitory actions on GIRK channels of dopamine neurons may be involved in the antidepressant-like effects of tipepidine. In this study, we generated GIRK2DATKO mice withGirk2/Kcnj6conditional deletion and assessed depression-related behavior of the mice. The Cre/loxPsystem was used to selectively delete GIRK2 subunit containing GIRK channels in the neurons expressing dopamine transporter. First, deletion of GIRK2 subunits in the ventral tegmental area (VTA) neurons expressing dopamine transporters was confirmed by hisitochemically and electrophysiologically. In the mice, a significant decrease in the immobility time of forced swimming test was observed. Locomotor activity of the mice was not changed compared to that of GIRK2floxedmice, when tested in the open field. These results suggest that the antidepressant-like effect of antitussives such as tipepidine may be caused partly through the inhibitory actions on GIRK channels in the dopamine neurons.