Decreased anxiety in mice lacking the organic cation transporter 3
Decreased anxiety in mice lacking the organic cation transporter 3
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DOI：
10.1007/s00702-009-0205-1
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发表时间：
2009-06-01
影响因子：
3.3
通讯作者：
Reif, Andreas
中科院分区：
文献类型：
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作者：
Wultsch, Thomas;Grimberg, Gundula;Reif, Andreas
有机阳离子转运蛋白3（OCT 3;同义词：神经元单胺转运蛋白，EMT，Slc 22 a3）编码有机阳离子转运蛋白的同种型，并且在整个脑中广泛表达。OCT是一类高容量、双向、多特异性的有机阳离子转运蛋白。这些还包括血清素、多巴胺和去甲肾上腺素，使得OCT成为包括焦虑症在内的各种神经精神障碍的有吸引力的候选者。OCT 3与中枢神经系统中单胺能信号传导的终止有关。然而，有趣的是，OCT 3 mRNA在5-羟色胺转运蛋白敲除小鼠的海马中也显著上调，在那里它可能作为5-羟色胺的替代再摄取机制。因此，检查OCT 3敲除小鼠的行为表型对于评估OCT 3的作用至关重要。因此，我们对缺乏OCT 3基因的小鼠进行了全面的行为测试。虽然在Morris水迷宫测试中的认知功能和用居民-入侵者范例测量的攻击水平与相应的对照动物在相同的范围内，OCT 3敲除动物显示出活动增加的趋势，并且与它们各自的野生型相比，在高架十字迷宫测试和旷场测试中焦虑显著减少。类型控制争论OCT 3在调节恐惧和焦虑中的作用，可能是通过调节边缘系统回路中的多巴胺能张力。
The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. OCTs are a family of high-capacity, bidirectional, multispecific transporters of organic cations. These also include serotonin, dopamine and norepinephrine making OCTs attractive candidates for a variety of neuropsychiatric disorders including anxiety disorders. OCT3 has been implicated in termination of monoaminergic signalling in the central nervous system. Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin. The examination of the behavioural phenotype of OCT3 knockout mice thus is paramount to assess the role of OCT3. We have therefore subjected mice lacking the OCT3 gene to a comprehensive behavioural test battery. While cognitive functioning in the Morris water maze test and aggression levels measured with the resident-intruder paradigm were in the same range as the respective control animals, OCT3 knockout animals showed a tendency of increased activity and were significantly less anxious in the elevated plus-maze test and the open field test as compared to their respective wild-type controls arguing for a role of OCT3 in the regulation of fear and anxiety, probably by modulating the serotonergic tone in limbic circuitries.