σ受体激动剂对大鼠学习记忆障碍的改善作用  

Effects of σ receptor agonists on learning and memory impairment in rats

作　　者：董爱梅 纪雪飞[2] 陆玲玲[2] 邹莉波[2] 

机构地区：[1]山东生物药物研究院,山东济南250608 [2]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2007年第5期298-302,共5页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(30070868)

摘　　要：目的考察σ受体激动剂对大鼠空间记忆功能的影响及对东莨菪碱所致大鼠新物体辨别功能障碍的改善作用。方法采用八方向放射状迷路及新物体辨别实验方法。结果σ1受体激动剂SA4503 0.3 mg.kg-1灌胃显著减少6 min延迟所致的工作记忆错误次数的增加,选择性σ1受体拮抗剂NE-100完全拮抗了SA4503的作用。σ1/σ2受体激动剂DTG(1.3-ditolyguanidine)有减少工作记忆错误的趋势,但无统计学意义。神经类固醇脱氢雄表酮硫酸酯(dehydroepiandrosterone sulfate,DHEAS)、孕烯醇酮硫酸酯(pregnenolone sulfate,PREGS)显著抑制东莨菪碱所致的新物体辨别率的降低,此作用可被σ1受体阻断剂孕酮(progesterone,PROG)所拮抗。DTG对动物新物体辨别障碍未见显著影响。结论SA4503、DHEAS及PREGS通过激动σ1受体发挥改善记忆功能的作用,σ1受体在学习记忆过程中发挥重要作用。Objective To investigate the effects of σ receptor agonists SA4503, 1.3-ditolyguanidine （DTG）and neuroactive steroids on learning and memory impairment in rats. Methods The radial arm maze task and the object recognition test were used. Results The results showed that the insertion of a 6-rain delay in the radial arm maze task caused a specific decline in working memory, but had no effect on reference memory. This decline in working memory was improved by σ1 receptor agonist SA4503, but not by the non-selective σ1/σ2 receptor agonist DTG. This ameliorating effect of SA4503 was completely attenuated by co-treatment with a selective σ1 receptor antagonist. The σ1 receptor agonists dehydroepiandrosterone sulfate（DHEAS）and pregnenolone sulfate （PREGS） allowed marked reversions of the object recognition deficits induced by the muscarinic acetycholine receptor antagonist scopolamine, which was completely antagonized by the σ1 receptor antagonist progesterone（PROG）. The non-selective σ1/σ2 receptor agonist DTG did not show any effect. Conclusion These results suggest that σ1 receptor plays an important role in learning and memory.

关 键 词：σ受体激动剂 1-[2-(3 4-二甲氧基苯基)乙基]4-(3-苯丙基)哌嗪(SA4503) 1 3-二(2-甲苯基胍)(DTG) 脱氢雄表酮硫酸酯 孕烯醇酮硫酸酯 学习记忆 

分 类 号：R96[医药卫生—药理学]