Background

Mitragynine, the major indole alkaloid from Mitragyna speciosa has been reported previously to possess abuse liability. However, there are insufficient data suggesting the mechanism through which this pharmacological agent causes addiction.

Aims

In this study, we investigated the effects of mitragynine on dopamine (DA) level and dopamine transporter (DAT) expression from the rat’s frontal cortex.

Methods

DA level was recorded in the brain samples of animals treated with acute or repeated exposure for 4 consecutive days with either vehicle or mitragynine (1 and 30 mg/kg) using electrochemical sensor. Animals were then decapitated and the brain regions were removed, snap-frozen in liquid nitrogen and immediately stored at −80 °C. DA level was quantified using Enzyme linked immunosorbent assay (ELISA) kits and DAT gene expression was determined using quantitative real time polymerase chain reaction (RT-qPCR).

Results/outcome

Mitragynine (1 and 30 mg/kg) did not increase DA release following acute treatment, however, after repeated exposure at day 4, mitragynine significantly and dose dependently increased DA release in the frontal cortex. In this study, we also observed a significant increase in DAT mRNA expression at day 4 in group treated with mitragynine (30 mg/kg).

Conclusion/interpretation

Data from this study indicates that mitragynine significantly increased DA release when administered repeatedly, increased in DAT mRNA expression with the highest tested dose (30 mg/kg). Therefore, the rewarding effects observed after mitragynine administration could be due to its ability to increase DA content in certain areas of the brain especially the frontal cortex.

中文翻译：

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由 mitragynine (Kratom) 诱发的多巴胺释放的实时监测：通过电化学传感器的洞察力

背景

Mitragynine 是来自Mitragyna speciosa的主要吲哚生物碱，此前曾有报道称其具有滥用倾向。然而，没有足够的数据表明这种药物引起成瘾的机制。

目标

在这项研究中，我们研究了 mitragynine 对大鼠额叶皮层多巴胺 (DA) 水平和多巴胺转运蛋白 (DAT) 表达的影响。

方法

使用电化学传感器在用载体或 mitragynine（1 和 30 mg/kg）连续 4 天急性或重复暴露治疗的动物的脑样本中记录 DA 水平。然后将动物斩首并取出大脑区域，在液氮中速冻并立即储存在-80°C。使用酶联免疫吸附测定 (ELISA) 试剂盒对 DA 水平进行量化，并使用定量实时聚合酶链式反应 (RT-qPCR) 确定 DAT 基因表达。

结果/结果

Mitragynine（1 和 30 mg/kg）在急性治疗后没有增加 DA 释放，然而，在第 4 天重复暴露后，mitragynine 显着且剂量依赖性地增加额叶皮质中的 DA 释放。在这项研究中，我们还观察到在用 mitragynine (30 mg/kg) 治疗的组中，第 4 天 DAT mRNA 表达显着增加。

结论/解释

该研究的数据表明，当重复给药时，mitragynine 显着增加 DA 释放，在最高测试剂量 (30 mg/kg) 下增加 DAT mRNA 表达。因此，在给予mitragynine 后观察到的有益效果可能是由于它能够增加大脑某些区域尤其是额叶皮层中的DA 含量。