格拉司琼对咯利普兰致呕吐、抗抑郁及增强学习记忆能力的影响  

Effects of granisetron on vomiting,anti-depression and memory enhancement potential of rolipram

作　　者：李国熊[1] 周涛[1] 周恒[1] 许重远[2] 徐江平[1] 

机构地区：[1]南方医科大学药学院神经药理学科,广东广州510515 [2]南方医科大学南方医院国家药物临床试验机构,广东广州510515

出　　处：《中国药理学与毒理学杂志》2011年第3期240-244,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30672453);国家自然科学基金资助项目(30973518)~~

摘　　要：目的评价格拉司琼(Gra)对咯利普兰(Rol)潜在致恶心呕吐反应的影响,同时考察Gra对Rol抗抑郁作用及增强空间学习记忆能力的影响。方法通过观察氯胺酮/赛拉嗪诱导的麻醉小鼠翻正反射恢复时间来间接评价Rol潜在的致恶心呕吐反应;采用强迫游泳实验、悬尾实验、Morris水迷宫考察Rol与Gra合用对小鼠抑郁样症状、空间学习记忆能力的影响。结果 Rol 0.5 mg·kg-1能显著地将氯胺酮/赛拉嗪诱导的小鼠翻正反射消失持续时间从麻醉对照组的(48.6±11.1)min降低至(30.0±8.6)min(P<0.01);Rol联合Gra 0.05,0.5和5 mg.kg-1后,小鼠麻醉时间分别延长至(39.5±15.5)min,(43.1±17.7)min(P<0.05)和(42.1±16.6)min(P<0.05)。单独Rol 0.5 mg·kg-1以及Rol联合Gra 0.05,0.5和5 mg.kg-1小鼠的游泳不动时间分别为133±52,135±66,93±36和(133±64)s,无统计学差异;悬尾不动时间分别为116±46,90±33,114±36和(120±59)s,无统计学差异。逃避潜伏期、穿越原平台次数及平台所在象限探索时间的比率Rol以及联合Gra组间无显著差异。结论 Gra能减轻Rol潜在的恶心呕吐反应,但是不影响Rol的抗抑郁、增强空间学习记忆能力的效应。OBJECTIVE To assess the anti-emetic potential of granisetron（Gra） on mice vomiting induced by rolipram（Rol） and the effect of Gra on anti-depression and spatial memory enhancement of Rol.METHODS The anti-emetic potential of Gra was evaluated based on the duration of anesthesia in mice induced by the combination of xylazine/ketamine,which was determined as the time between the loss and regaining of the righting reflex.The depression models（forced swimming test and tail suspension test） and Morris water maze were used to assess the anti-depression and cognitive enhancement effects with the combination of Gra and Rol.RESULTS Rol 0.5 mg·kg^-1significantly reduced duration of anesthesia induced by xylazine/ketamine in KM mice from（48.6±11.1）min to（30.0±8.6）min（P〈0.05）.Then Rol combined with Gra 0.05,0.5 and 5 mg·kg^-1increased the duration of anesthesia compared with Rol as（39.5±15.5）min,（43.1±17.7）min（P〈0.05） and（42.1±16.6） min（P〈0.05）.Forced swimming test and tail suspension test data showed Rol combined with Gra did not influence the immobility time.Meanwhile,Rol combined with Gra did not influence spatial memory performance in Morris water maze.CONCLUSION Rol combined with Gra can significantly reduce the emetic potential of Rol,without intervention in its antidepressant effects or cognitive enhancement.So the combination of Rol and Gra is a potential effective treatment for nausea and vomiting in pharmacodynamics.

关 键 词：咯利普兰 格拉司琼 恶心呕吐 抗抑郁 学习记忆 联合用药 

分 类 号：R969[医药卫生—药理学]