米特拉基宁 (克拉托姆) - 戒断行为和认知障碍可以通过表观遗传机制改善
Suleiman Yunusa1,2, Christian P Müller1,3,4, Zurina Hassan1
1Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia.
British journal of pharmacology
|March 25, 2024
概括
克拉 (mitragynine) 戒断会通过改变海马的可塑性和表观遗传标记物引起认知缺陷. 一种组织素脱乙酶抑制剂SAHA逆转了这些效应,这表明了对Kratom成的新治疗方法.
科学领域:
- 神经药理学神经药理学
- 成研究 研究成研究
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 克拉来自Mitragyna speciosa,在全球范围内被用作一种天然疗法.
- 过度消费Kratom可以导致类似成的症状,包括戒断和认知障碍.
- 米特拉金因是克拉的主要化物,表现出类似阿片类药物的效应.
研究的目的:
- 在大鼠中调查米特拉基尼因撤销的神经药理学影响.
- 为了比较米特拉基尼因戒断与吗啡戒断.
- 为了确定潜在的药理疗法,用于认知缺陷与米特拉基宁撤销相关.
主要方法:
- 鼠被用米特拉基尼或吗啡治疗了14天.
- 行为测试评估了戒断症状和认知功能 (被动回避任务).
- 在海马组织上进行了电生理学记录 (fEPSP,LTP) 和表观遗传标记分析 (基因组表达,HDAC2).
主要成果:
- 米特拉基宁戒断诱导了与吗啡戒断类似的剂量依赖行为征兆.
- 米特拉基宁的戒断导致认知功能受损,海马长期潜能 (LTP) 降低.
- 作为HDAC抑制剂的SAHA可以逆转米特拉基尼因戒断引起的表观遗传变化,海马功能障碍和认知缺陷,但恶化了吗啡戒断效应.
结论:
- 表观遗传变化和海马体可塑性改变可能是米特拉基尼因戒断引起的认知障碍的基础.
- 这些发现表明一种潜在的治疗策略,针对Kratom/mitragynine戒断和成的表观遗传修饰.
- 观察到的SAHA的差异性影响突出显示了米特拉基宁和吗啡戒断之间的独特机制.
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