Yusoff Nurul H M, Mansor Sharif M, Müller Christian P, Hassan Zurina
Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.
Behav Brain Res. 2017 Aug 14;332:1-6. doi: 10.1016/j.bbr.2017.05.059. Epub 2017 May 27.
Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats. In the first experiment we tested the effects of the opiate receptor antagonist naloxone (0.1, 0.3 and 1.0mg/kg) on the acquisition of mitragynine (10mg/kg)-induced CPP. In the second experiment, we tested the involvement of opiate receptors in the expression of mitragynine-induced CPP in rats. We found that naloxone suppresses the acquisition of mitragynine-induced CPP. This effect was already evident at a dose of naloxone (0.1mg/kg) which, by itself, had no conditioned place aversion (CPA) effect. Higher doses of naloxone induced a CPA and blocked mitragynine-induced CPP. In contrast, naloxone had no effect on the expression of mitragynine-induced CPP. These findings suggest that the acquisition, but not the expression of the reinforcing effects of mitragynine is mediated by opiate receptors.
帽柱木碱是草药制剂 kratom（也叫 ketum）中的主要精神活性成分，kratom 源自植物美丽帽柱木。kratom 在东南亚是一种广泛滥用的药物，低至中等剂量时有精神兴奋作用，而高剂量时有阿片样物质作用。已表明帽柱木碱具有阿片受体亲和力。然而，其在帽柱木碱行为效应中的作用尚不清楚。在此，我们使用大鼠条件性位置偏爱（CPP）范式来探究帽柱木碱的强化作用是否由阿片受体介导。在第一个实验中，我们测试了阿片受体拮抗剂纳洛酮（0.1、0.3 和 1.0mg/kg）对帽柱木碱（10mg/kg）诱导的 CPP 获得的影响。在第二个实验中，我们测试了阿片受体在大鼠帽柱木碱诱导的 CPP 表达中的作用。我们发现纳洛酮抑制了帽柱木碱诱导的 CPP 的获得。这种效应在纳洛酮剂量为 0.1mg/kg 时就已很明显，而该剂量本身并无条件性位置厌恶（CPA）效应。更高剂量的纳洛酮诱导了 CPA 并阻断了帽柱木碱诱导的 CPP。相比之下，纳洛酮对帽柱木碱诱导的 CPP 的表达没有影响。这些发现表明，帽柱木碱强化作用的获得而非表达是由阿片受体介导的。
