Ren Baolan, Zhou Zhijie, Liu Zhuguo, Li Bailin, Ou Jie, Dai Qiuyun
College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, PR China; Beijing Institute of Biotechnology, Beijing 100071, PR China.
Beijing Institute of Biotechnology, Beijing 100071, PR China.
Neurosci Lett. 2015 Jun 15;597:38-42. doi: 10.1016/j.neulet.2015.04.023. Epub 2015 Apr 17.
As a variant of peptide conantokin-T (con-T), con-T[M8Q] is derived from the venom of Conus tulipa. Our previous study has demonstrated that con-T[M8Q] selectively targets N-methyl-d-aspartate receptor (NMDAR) NR2B subunit. In the present study, we determined the effects of con-T[M8Q] on the expression and development of morphine tolerance using hot plate test and acetic acid writhing test. Our results demonstrated that con-T[M8Q] could efficiently attenuate the expression and development of morphine analgesic tolerance in mice at low doses (5-20nmol/kg), and it exhibited more potent effects compared with ifenprodil, a typical small-molecule antagonist of NMDAR. In addition, low doses of con-T[M8Q] (5-20nmol/kg) did not cause drug resistance and apparent analgesic activity compared with morphine. Taken together, con-T[M8Q] could be a promising new candidate in attenuating morphine tolerance.
作为肽类芋螺毒素-T（con-T）的一种变体，con-T[M8Q]源自郁金香芋螺的毒液。我们之前的研究表明，con-T[M8Q]选择性靶向N-甲基-D-天冬氨酸受体（NMDAR）的NR2B亚基。在本研究中，我们使用热板试验和醋酸扭体试验确定了con-T[M8Q]对吗啡耐受性表达和发展的影响。我们的结果表明，低剂量（5-20nmol/kg）的con-T[M8Q]可有效减弱小鼠吗啡镇痛耐受性的表达和发展，与典型的NMDAR小分子拮抗剂艾芬地尔相比，它表现出更强的作用。此外，与吗啡相比，低剂量的con-T[M8Q]（5-20nmol/kg）不会引起耐药性和明显的镇痛活性。综上所述，con-T[M8Q]可能是减轻吗啡耐受性的一种有前景的新候选物。
