Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Psychopharmacology (Berl). 2021 Nov;238(11):3183-3191. doi: 10.1007/s00213-021-05934-4. Epub 2021 Aug 1.
Kratom (Mitragyna speciosa Korth), a native medicinal plant of Southeast Asia, is proposed to exhibit potential therapeutic value as an opioid substitute. However, studies of its negative emotional states resulting from withdrawal particularly of its main psychoactive compound, mitragynine (MG), are limited.
Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus.
Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16 mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9 days and withdrawal was precipitated on the tenth day using naloxone (1 mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24 h after the last dose of MG or morphine administration.
Unlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45 mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points.
These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder.
Kratom（Mitragyna speciosa Korth），一种东南亚本土药用植物，被认为具有作为阿片类药物替代物的潜在治疗价值。然而，关于其主要精神活性化合物——mitragynine（MG）戒断后负面情绪状态的研究有限。
本研究采用戊四氮（PTZ）辨别试验，旨在研究 MG 对 PTZ 刺激的反应作用，并评估 MG 戒断对 PTZ 刺激的泛化效应。
将 20 只大鼠（n=20）通过食物强化（FR-10，VI-15）序贯方案进行训练，在给予致焦虑化合物 PTZ（16mg/kg，ip）后按压一个杠杆，在给予载体后按压另一个杠杆。急性试验后，暂停训练，大鼠每天 8 小时间隔接受 MG 或吗啡慢性治疗，第 10 天用纳洛酮（1mg/kg，ip）引发戒断。在最后一次 MG 或吗啡给药后 2、8 和 24 小时，测试大鼠对 PTZ 的泛化作用。
与产生剂量相关的 PTZ 样刺激的吗啡不同，3、10、30 和 45mg/kg 剂量的 MG 对 PTZ 辨别刺激无替代作用。与吗啡产生时间依赖性的 PTZ 刺激泛化相反，纳洛酮未在 MG 处理的大鼠中引发戒断效应，因为它们在三个戒断时间点都选择了载体杠杆。
这些结果表明，MG 对吗啡戒断产生了非常不同的反应，与焦虑样主观症状无关。MG 的这些特征可能为将其用作治疗阿片类药物使用障碍的新型药物治疗干预措施提供进一步支持。
