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中国临床药理学与治疗学 ›› 2000, Vol. 5 ›› Issue (1): 6-9.

• 论著 • 上一篇    下一篇

四氢孕酮和地西泮对暴露于架高十字迷宫小鼠的作用

于榕, 鲁映青, 盛美萍, 史念慈, 姚明辉   

  1. 上海医科大学基础医学院药理教研室,上海 200032
  • 收稿日期:2000-02-10 出版日期:2000-03-26 发布日期:2020-11-26

Comparison of anxiolytic effects of allopregnanolone and diazepam on the elevated plus-maze in mice

YU Rong , LU Ying-Qing, SHENG Mei-Ping, SHI Nian-Ci, YAO Ming-Hui   

  1. Department of Pharmacology,Shanghai Medical University,Shanghai 200032
  • Received:2000-02-10 Online:2000-03-26 Published:2020-11-26
  • About author:YU Rong,male,35 years old,Ph.D,as sociate professor,neurop harmacology.

摘要: 目的 比较孕酮的还原性代谢产物四氢孕酮和地西泮抗焦虑作用。方法 C57小鼠腹腔注射四氢孕酮 、地西泮或赋形剂,20 min 后观察在架高十字迷宫试验中的表现,测定其自发活动 。结果 腹腔注射四氢孕酮 0.1mg·kg-1,明显缩短小鼠进入十字迷宫开臂的潜伏期[ 从(31.30±8.39)s 减少到 (8.80±6.00)s,P<0.001],并显著增加进入十字迷宫开臂的次数 (从 1.20±0.42 增到4.80±1.75,P<0.001) 及在开臂的滞留时间占总时间的百分比 (从 7.13%增加到 32.50%,P<0.001) 。而腹腔注射地西泮 0.25 mg·kg-1的抗焦虑作用弱于四氢孕酮 。自发活动实验显示,0.5 mg·kg-1地西泮明显减少小鼠自发活动 (P<0.01),而 0.1mg·kg-1地西泮和 0.25 mg·kg-1的四氢孕酮均不影响小鼠自发活动。结论 试验结果提示神经甾体和地西泮对小鼠行为有不同的作用 。四氢孕酮具选择性抗焦虑作用而不影响自发活动,可望成为地西泮抗焦虑的代用品。

关键词: 四氢孕酮, 地西泮, 焦虑, 抗焦虑, 十字迷宫, 自发活动

Abstract: Aim To compare the anxiolytic effects of reduced metabolite of progesterone and benzodi-azepine.Methods The effects of allopregnanolone and diazepam on spontaneous locomotor activity and on exploration in the elevated plus-maze were studied in C57 mice 20 min after vehicle or drug intraperitoneal administration.Results Allopregnanolone (0.1mg·kg-1,ip)elicited marked anxiolytic effects in terms of significantly reducing the latency to enter the open arm from (31.30±8.39)s to (8.80±6.00)s,(P<0.001),and significantly increasing both the number of open arm entries from 1.20±0.42 to 4.80±1.75,(P<0.001)and the proportion of total time spent on the open arm from 7.13%to 32.50%,(P<0.001).Mean-while,the diazepam (0.25mg·kg-1)produced a lower anxiolytic effect comparing to that of the allopregnanolone.Analysis of spontaneous locomotor activity showed while 0.5mg·kg-1of diazepam decreased the locomotor activity (P<0.01),neither 0.1mg·kg-1of allopreg-nanolonenor 0.25mg·kg-1of diazepam affect the locomotor activity score.Conclusion Together,these results provide evidence for differential behavioral actions of the neurosteroids and benzodiazepines.Since the allopregnanolone produce a selective anxiolytic effect without affecting the spontaneous locomotor activity,the allopregnanolone may be a better alternative for diazepam in treating anxiety.

Key words: allopregnanolone, diazepam, anxiety, elevated plus-maze, anxiolytic, sponta-neous locomotor activity