Yusoff Nurul H M, Mansor Sharif M, Müller Christian P, Hassan Zurina
Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.
Behav Brain Res. 2018 Jun 1;345:65-71. doi: 10.1016/j.bbr.2018.02.039. Epub 2018 Feb 27.
Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA receptor.
帽柱木碱是在原产于东南亚的茜草科植物美丽帽柱木的叶子中发现的主要生物碱。由于其具有精神兴奋和阿片样作用,这种化合物一直被用于传统用途或消遣用途。最近,帽柱木碱已被证明能产生条件性位置偏爱(CPP),表明美丽帽柱木具有奖赏和动机性质。在此,使用大鼠的CPP范式研究了GABA受体在介导帽柱木碱奖赏中的作用。首先,我们研究了GABA受体激动剂巴氯芬(1.25、2.5和5毫克/千克)对帽柱木碱(10毫克/千克)诱导的CPP获得的影响。其次,测试了GABA受体在帽柱木碱诱导的CPP表达中的作用。我们发现,较高剂量(2.5和5毫克/千克)的巴氯芬可阻断帽柱木碱诱导的CPP的获得。高剂量的巴氯芬抑制运动活动并引起CPP。此外,我们发现巴氯芬(2.5和5毫克/千克)也阻断了帽柱木碱诱导的CPP的表达。这些发现表明,帽柱木碱强化特性的获得和表达均受GABA受体控制。