Antidepressant-like effects of piperine and its derivative, antiepilepsirine
Antidepressant-like effects of piperine and its derivative, antiepilepsirine
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DOI：
10.1080/10286020500384302
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发表时间：
2007-01-01
影响因子：
1.7
通讯作者：
Wang, Min-Wei
中科院分区：
文献类型：
--
作者：
Li, Song;Wang, Che;Wang, Min-Wei
在本研究中，在两种抑郁模型中研究了胡椒碱（PIP）及其衍生物抗癫痫碱（AES）的抗抑郁样作用：强迫游泳试验（FST）和悬尾试验（TST）。为了进一步探讨其抗抑郁样活性的机制，还测定了脑单胺水平以及单胺氧化酶 A 和 B（MAO-A 和 MAO-B）活性。研究结果首次表明，长期服用两周后，10-20mg/kg剂量的PIP和AES显着缩短了FST和TST中的不动持续时间，而旷场测试中的运动活动没有随之变化。但在80 mg/kg剂量下，PIP和AES的抗抑郁活性在TST和FST中均恢复至对照水平。在单胺测定中，长期服用 AES 显着升高了纹状体、下丘脑和海马中的多巴胺水平，并且还增加了下丘脑和海马中的血清素水平。相比之下，PIP的长期治疗仅提高下丘脑和海马的血清素水平，但不影响多巴胺水平。此外，PIP 和 AES 对这些大脑区域的去甲肾上腺素水平没有影响。 MAO 活性测定还表明，PIP 和 AES 显示出较小的 MAO 抑制活性。在本研究中，我们证明 PIP 和 AES 的抗抑郁样作用可能取决于神经递质合成的增强或神经递质再摄取的减少。 PIP 的抗抑郁特性被认为是通过调节血清素能系统来介导的，而 AES 的抗抑郁作用机制可能是由于其对血清素能系统和多巴胺能系统的双重调节。
In the present study, antidepressant- like effects of piperine ( PIP) and its derivative, antiepilepsirine ( AES), were investigated in two depressive models: forced swimming test ( FST) and tail suspension test ( TST). To further explore the mechanisms underlying their antidepressant- like activities, the brain monoamine levels and monoamine oxidase A and B ( MAO- A and MAO- B) activities were also determined. The research results for the first time indicated that after two weeks of chronic administration, PIP and AES at doses of 10 - 20 mg/ kg significantly reduced the duration of immobility in both FST and TST, without accompanying changes in locomotor activity in the open- field test. But at the dose of 80 mg/ kg, the antidepressant activity of both PIP and AES returned to the control level in the TST and FST. In the monoamine assay, chronic AES administration significantly elevated the dopamine level in striatum, hypothalamus and hippocampus, and also increased the serotonin level in the hypothalamus and hippocampus. In contrast, chronic treatment of PIP only enhanced the serotonin level in the hypothalamus and hippocampus but did not influence the dopamine level. Moreover, both PIP and AES showed no effects on level of noradrenaline in these brain regions. The MAO activity assay also indicated that PIP and AES showed a minor MAO inhibitory activity. In the present study, we demonstrated that the antidepressant- like effects of PIP and AES might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake. Antidepressant properties of PIP were supposed to be mediated via the regulation of serotonergic system, whereas the mechanisms of antidepressant action of AES might be due to its dual regulation of both serotonergic and dopaminergic systems.