四氢孕酮和地西泮对暴露于架高十字迷宫小鼠的作用(英文)  

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

作　　者：于榕[1] 鲁映青[1] 盛美萍[1] 史念慈[1] 姚明辉[1] 

机构地区：[1]上海医科大学基础医学院药理教研室,上海200032

出　　处：《中国临床药理学与治疗学》2000年第1期6-9,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

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 ,20min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0.25mg·kg-1的抗焦虑作用弱于四氢孕酮。自发活动实验显示 ,0.5mg·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0.25mg·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 。Aim To compare the anxiolytic effects of reduced metabolite of progesterone and benzodiazepine.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 (0.1 mg·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). Meanwhile, the diazepam (0.25 mg·kg-1) produced a lower anxiolytic effect comparing to that of the allopregnanolone. Analysis of spontaneous locomotor activity showed while 0.5 mg·kg-1 of diazepam decreased the locomotor activity (P<0.01),neither 0.1 mg·kg-1 of allopregnanolone nor 0.25 mg·kg-1 of 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.

关 键 词：四氢孕酮 地西泮 焦虑 抗焦虑 十字迷宫 自发活动 

分 类 号：R977.12[医药卫生—药品] R749.7[医药卫生—药学]