Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization
Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization
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DOI：
10.1016/j.bbr.2015.02.012
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发表时间：
2015-05-01
影响因子：
2.7
通讯作者：
Takahama, Kazuo
中科院分区：
文献类型：
--
作者：
Hamao, Keiko;Kawaura, Kazuaki;Takahama, Kazuo
我们之前报道过，蒂哌定的新型抗抑郁样作用可能至少部分是通过抑制G蛋白偶联的内校正钾通道激活中边缘多巴胺神经元而产生的。在这项研究中，我们使用体内微透析技术研究了替佩定是否会增加大鼠伏隔核（NAc）中的多巴胺水平。我们进一步评估了抗抑郁药样有效剂量的替佩定是否会诱导大鼠运动活动的行为和交叉致敏。我们发现，在自由运动的大鼠中，急性给药替佩定会增加NAc中的多巴胺水平，但不会增加运动活动。抗抑郁药样有效剂量（20和40 mg/kg， ig）的替佩定未引起大鼠行为致敏。此外，在大鼠中没有观察到替佩定和甲基苯丙胺之间的交叉致敏。这些结果进一步支持了我们的工作假设，即蒂佩定可能通过激活腹侧被盖区- nac多巴胺能神经元产生一种新的抗抑郁样作用，其机制与成瘾药物的强化作用不同。(C) 2015 Elsevier B.V.版权所有
We previously reported that the novel antidepressant-like effect of tipepidine may be produced at least partly through the activation of mesolimbic dopamine neurons via inhibition of G protein-coupled inwardly rectifying potassium channels. In this study, we investigated whether tipepidine increases dopamine levels in the nucleus accumbens (NAc) in rats using an in vivo microdialysis technique. We further assessed whether tipepidine at antidepressant-like effective doses induces behavioral- and cross-sensitization of locomotor activity in rats using the open field test. We found that acute administration of tipepidine increased dopamine levels in the NAc in freely moving rats without increasing locomotor activity. Tipepidine at antidepressant-like effective doses (20 and 40 mg/kg, i.p.) did not cause behavioral sensitization in rats. Furthermore, cross-sensitization between tipepidine and methamphetamine was not observed in rats. These results further support our working hypothesis that tipepidine may produce a novel antidepressant-like effect through activation of ventral tegmental area-NAc dopaminergic neurons whose mechanisms differ from those contributing to the reinforcing effects of addictive drugs. (C) 2015 Elsevier B.V. All rights reserved.