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美沙酮条件性位置偏爱模型中,来源于越南黄桐(Mitragyna speciosa (Korth.) Havil.)的生物碱提取物的改善作用。

Ameliorative effects of alkaloid extract from Mitragyna speciosa (Korth.) Havil. Leaves on methamphetamine conditioned place preference in mice.

机构信息

Physiology Program, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hatyai Campus, Hatyai, Songkhla, 90112, Thailand; Biosignal Research Center for Health, Faculty of Science, Prince of Songkla University, Hatyai Campus, Hatyai, Songkhla, 90112, Thailand.

Biology Program, Division of Biological Science, Faculty of Science, Prince of Songkla University, Hatyai Campus, Hatyai, Songkhla, 90112, Thailand; Biosignal Research Center for Health, Faculty of Science, Prince of Songkla University, Hatyai Campus, Hatyai, Songkhla, 90112, Thailand.

出版信息

J Ethnopharmacol. 2022 Feb 10;284:114824. doi: 10.1016/j.jep.2021.114824. Epub 2021 Nov 8.

DOI:10.1016/j.jep.2021.114824
PMID:34763040
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Mitragyna speciosa (Korth.) Havil., popularly known as Kratom (KT), is a medicinal plant used for pain suppression in Southeast Asia. It has been claimed to assist drug users withdraw from methamphetamine (METH) dependence. However, its use was controversial and not approved yet.

AIM OF THE STUDY

This study was conducted to characterize local field potential (LFP) patterns in the nucleus accumbens (NAc) and the hippocampus (HP) in mice with METH conditioned place preference (CPP) that were treated with KT alkaloid extract.

MATERIALS AND METHODS

Male Swiss albino ICR mice were implanted with intracraneal electrodes into the NAc and HP. To induce METH CPP, animals were injected intraperitoneally once a day with METH (1 mg/kg) and saline (0.9% w/v) alternately and put into METH/saline compartments to experience the associations between drug/saline injection and the unique environmental contexts for 10 sessions. Control group received saline injection paired with both saline/saline compartments. On post-conditioning day, effects of 40 (KT40), 80 (KT80) mg/kg KT alkaloid extract and 20 mg/kg bupropion (BP) on CPP scores and LFP powers and NAc-HP coherence were tested.

RESULTS

Two-way ANOVA revealed significant induction of CPP by METH sessions (P < 0.01). Multiple comparisons indicated that METH CPP was completely abolished by KT80 (P < 0.001). NAc gamma I (30.0-44.9 Hz) and HP delta (1.0-3.9 Hz) powers were significantly increased in mice with METH CPP (P < 0.01). The elevated NAc gamma I was significantly suppressed by KT80 (P < 0.05) and the increased HP delta was significantly reversed by KT40 (P < 0.01) and KT80 (P < 0.001). In addition, NAc-HP coherence was also significantly increased in gamma I (30.0-44.9 Hz) frequency range (P < 0.05) but it was reversed by KT80 (P < 0.05). Treatment with BP did not produce significant effect on these parameters.

CONCLUSIONS

These findings demonstrated that KT alkaloid extract significantly reversed CPP scores and LFP patterns induced by METH administration. The ameliorative effects of the extract might be beneficial for treatment of METH craving and addiction.

摘要

民族药理学相关性

Mitragyna speciosa(Korth.)Havil.,俗称 Kratom(KT),是一种药用植物,用于东南亚的止痛。据称,它有助于吸毒者戒除甲基苯丙胺(METH)依赖。然而,它的使用存在争议,尚未获得批准。

研究目的

本研究旨在研究 KT 生物碱提取物对甲基苯丙胺条件性位置偏爱(CPP)诱导的小鼠伏隔核(NAc)和海马(HP)局部场电位(LFP)模式的特征。

材料和方法

雄性瑞士白化 ICR 小鼠颅内植入 NAc 和 HP 电极。为了诱导 METH CPP,动物每天腹腔注射 METH(1mg/kg)和生理盐水(0.9%w/v)交替,放入 METH/生理盐水隔室,以体验药物/生理盐水注射与独特环境背景之间的关联,共 10 个疗程。对照组接受生理盐水注射,并与生理盐水/生理盐水隔室配对。在条件后一天,测试 40(KT40)、80(KT80)mg/kg KT 生物碱提取物和 20mg/kg 安非他酮(BP)对 CPP 评分、LFP 功率和 NAc-HP 相干性的影响。

结果

双向方差分析显示 METH 疗程显著诱导 CPP(P<0.01)。多重比较表明,KT80 完全消除了 METH CPP(P<0.001)。METH CPP 小鼠的 NAc 伽马 I(30.0-44.9Hz)和 HP 德尔塔(1.0-3.9Hz)功率显著增加(P<0.01)。KT80 显著抑制升高的 NAc 伽马 I(P<0.05),KT40 和 KT80 显著逆转升高的 HP 德尔塔(P<0.01 和 P<0.001)。此外,在伽马 I(30.0-44.9Hz)频率范围内,NAc-HP 相干性也显著增加(P<0.05),但被 KT80 逆转(P<0.05)。BP 治疗对这些参数没有产生显著影响。

结论

这些发现表明,KT 生物碱提取物显著逆转了 METH 给药引起的 CPP 评分和 LFP 模式。提取物的改善作用可能有益于治疗 METH 成瘾。

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