Manus James P, Crenshaw Rebecca C, Ringer Lindsay C, Towers Shelby A, Paige Nick B, Leon Francisco, McCurdy Christopher R, Lester Deranda B
Department of Psychology University of Memphis USA.
Department of Medicinal Chemistry University of Florida USA.
Neurosci Lett. 2025 Feb 28;850:138153. doi: 10.1016/j.neulet.2025.138153. Epub 2025 Feb 7.
Kratom is derived from the leaves of a plant (Mitragyna speciosa) native to Southeast Asia that has been consumed for its complex stimulant-like effects at low doses, opiate-like effects at high doses, to treat mood related issues like anxiety or depression, or to help ameliorate opioid withdrawal symptoms. However, the neural mechanisms of its major psychoactive alkaloids, mitragynine (MG) and 7-hydroxymitragynine (7-HMG), are still not clear. Given that the effects of kratom are often compared to drugs with abuse liabilities, the current study examined the effects of MG and 7-HMG on reward-related neurotransmission. Fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice before and after MG (1, 15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle. MG reduced dopamine release over the recording period (90 min) in a dose dependent manner, and the low dose of MG significantly increased dopamine autoreceptor functioning in males. Both sexes responded similarly to 7-HMG with the low dose of 7-HMG increasing dopamine release while the high dose decreased dopamine release. 7-HMG did not alter dopamine autoreceptor functioning for either sex. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine. Findings suggest that these kratom alkaloids do alter dopamine functioning, although potentially not in a way consistent with classic drugs of abuse. Further investigation of the neural mechanisms of kratom's alkaloids will provide crucial and urgent insight into their therapeutic uses or potential abuse liability.
kratom 源自东南亚一种植物（帽柱木属）的叶子，人们食用它是因其低剂量时有类似兴奋剂的复杂作用、高剂量时有类似阿片类药物的作用，用于治疗焦虑或抑郁等情绪相关问题，或帮助缓解阿片类药物戒断症状。然而，其主要精神活性生物碱——帽柱木碱（MG）和 7-羟基帽柱木碱（7-HMG）的神经机制仍不清楚。鉴于 kratom 的作用常与有滥用倾向的药物相比较，本研究考察了 MG 和 7-HMG 对奖赏相关神经传递的影响。采用固定电位安培法，在给予 MG（1、15 或 30mg/kg 腹腔注射）、7-HMG（0.5、1 或 2mg/kg 腹腔注射）或溶剂前后，对麻醉的雄性和雌性小鼠伏隔核（NAc）中刺激诱发的阶段性多巴胺释放进行定量。MG 在记录期（90 分钟）内以剂量依赖性方式减少多巴胺释放，低剂量的 MG 显著增加雄性小鼠多巴胺自身受体功能。两性对 7-HMG 的反应相似，低剂量的 7-HMG 增加多巴胺释放，而高剂量则减少多巴胺释放。7-HMG 对两性的多巴胺自身受体功能均无影响。MG 和 7-HMG 均未改变刺激诱发多巴胺的清除率。研究结果表明，这些 kratom 生物碱确实会改变多巴胺功能，尽管可能与经典滥用药物的方式不一致。对 kratom 生物碱神经机制的进一步研究将为其治疗用途或潜在滥用倾向提供关键且迫切的见解。
