Behavioral changes following antisense oligonucleotide-induced reduction of organic cation transporter-3 in mice
Behavioral changes following antisense oligonucleotide-induced reduction of organic cation transporter-3 in mice
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DOI：
10.1016/j.neulet.2005.03.014
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发表时间：
2005-07-01
影响因子：
2.5
通讯作者：
Hasegawa, T
中科院分区：
文献类型：
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作者：
Kitaichi, K;Fukuda, M;Hasegawa, T
有机阳离子转运蛋白 3 (OCT3) 可以转运单胺，类似于神经元单胺转运蛋白。然而，由于缺乏选择性配体，OCT3 的功能作用仍不清楚。因此，我们研究了反义 OCT3 (AS) 对小鼠的行为影响。 AS（0.075-0.25μg/0.25μl/h，持续7天）剂量依赖性地减少不动时间。此外，尽管AS（0.075μg/0.25μl/h，持续7天）或丙咪嗪（4mg/kg，腹腔注射）均无效，但丙咪嗪（4mg/kg，腹腔注射）显着缩短了用AS（0.075μg/0.25μl/h，持续7天）治疗的小鼠的不动时间。此外，AS（0.25μg/0.25μl/h，持续7天）显着增加甲基苯丙胺（1mg/kg，s.c.）诱导的运动活动，但不影响自发运动活动。这些结果表明OCT3可能成为治疗抑郁症和其他与单胺能神经系统相关疾病的新分子靶点。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
The organic cation transporter-3 (OCT3) can transport monoamines, similar to neuronal monoamine transporters. Due to the lack of selective ligands, however, the functional role of OCT3 is still unknown. Thus, we investigated behavioral effects of antisense against OCT3 (AS) in mice. AS (0.075-0.25 mu g/0.25 mu l/h, for 7 days) dose-dependently decreased immobility time. Moreover, although neither AS (0.075 mu g/0.25 mu l/h, for 7 days) or imipramine (4 mg/kg, i.p.) were effective, imipramine (4 mg/kg, i.p.) significantly decreased immobility time in mice treated with AS (0.075 mu g/0.25 mu l/h, for 7 days). Additionally, AS (0.25 mu g/0.25 mu l/h, for 7 days) significantly increased locomotor activity induced by methamphetamine (1 mg/kg, s.c.), but did not affect spontaneous locomotor activity. These result, suggest that OCT3 might become a novel molecular target to treat depression and other diseases related to monoaminergic neuronal systems. (c) 2005 Elsevier Ireland Ltd. All rights reserved.