Harun Norsyifa, Hassan Zurina, Navaratnam Visweswaran, Mansor Sharif M, Shoaib Mohammed
Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Psychopharmacology (Berl). 2015 Jul;232(13):2227-38. doi: 10.1007/s00213-015-3866-5. Epub 2015 Jan 25.
Mitragynine (MG) is the primary active alkaloid extracted from the leaves of Mitragyna speciosa or kratom and exhibits pharmacological activities mediated by opioid receptors. The plant has been traditionally used for its opium and psychostimulant-like effects to increase work efficiency or as a substitute in the self-treatment of opiate addiction.
The present study was performed to investigate the discriminative stimulus effects of MG in rats. The pharmacological mechanism of MG action and its derivative, 7-hydroxymitragynine (7-HMG) with a specific focus on opioid receptor involvement was examined in rats trained to discriminate morphine from vehicle. In order to study the dual actions of MG, the effect of cocaine substitution to the MG discriminative stimulus was also performed in MG-trained rats.
Male Sprague Dawley rats were trained to discriminate MG from vehicle in a two-lever drug discrimination procedure under a tandem variable-interval (VI 60') fixed-ratio (FR 10) schedule of food reinforcement.
Rats acquired the MG discrimination (15.0 mg/kg, i.p.) which was similar to the acquisition of morphine discrimination (5.0 mg/kg, i.p.) in another group of rats. MG substituted fully to the morphine discriminative stimulus in a dose-dependent manner, suggesting pharmacological similarities between the two drugs. The administration of 7-HMG derivative in 3.0 mg/kg (i.p.) dose engendered full generalisation to the morphine discriminative stimulus. In addition, the MG stimulus also partially generalised to cocaine (10.0 mg/kg, i.p.) stimulus.
The present study demonstrates that the discriminative stimulus effect of MG possesses both opioid- and psychostimulant-like subjective effects.
帽柱木碱（MG）是从帽柱木属植物或 kratom 的叶子中提取的主要活性生物碱，具有由阿片受体介导的药理活性。该植物传统上因其鸦片样和精神兴奋样作用而被用于提高工作效率，或作为阿片类药物成瘾自我治疗的替代品。
本研究旨在研究 MG 对大鼠的辨别刺激作用。在训练大鼠区分吗啡和溶剂的实验中，研究了 MG 及其衍生物 7-羟基帽柱木碱（7-HMG）的药理作用机制，特别关注阿片受体的参与情况。为了研究 MG 的双重作用，还在接受 MG 训练的大鼠中进行了可卡因替代 MG 辨别刺激的实验。
雄性 Sprague Dawley 大鼠在串联可变间隔（VI 60'）固定比率（FR 10）的食物强化时间表下，通过双杠杆药物辨别程序训练以区分 MG 和溶剂。
大鼠学会了区分 MG（腹腔注射 15.0 mg/kg），这与另一组大鼠学会区分吗啡（腹腔注射 5.0 mg/kg）的情况相似。MG 以剂量依赖性方式完全替代了吗啡的辨别刺激，表明这两种药物在药理上具有相似性。腹腔注射 3.0 mg/kg 剂量的 7-HMG 衍生物可完全泛化到吗啡辨别刺激。此外，MG 刺激也部分泛化到可卡因（腹腔注射 10.0 mg/kg）刺激。
本研究表明，MG 的辨别刺激作用具有阿片样和精神兴奋样主观效应。
