Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats

Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats
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DOI:
10.1007/s00213-003-1727-0
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发表时间:
2004-04-01
期刊:
影响因子:
3.4
通讯作者:
Kamei, C
Kamei, C
中科院分区:
医学3区
文献类型:
--
作者:
Shinomiya, K;Shigemoto, Y;Kamei, C

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基本原理。新的大鼠睡眠障碍模型可用于评估某些催眠药的特性。目标。本研究采用三种催眠药,即短效苯二氮卓类药物(三唑仑)、中效苯二氮卓类药物(氟硝基安定)和长效巴比妥类药物(苯巴比妥),将大鼠置于悬浮在水面上的栅格上,以探讨睡眠障碍模型的实用性。方法:研究方法。将测量脑电和肌电的电极植入大鼠的额叶皮质和背颈肌。用脑电图仪记录脑电和肌电。脑电和肌电分析采用SleepSign Ver.2.0。测量总觉醒时间、非快速眼动睡眠时间和快速眼动睡眠时间,时间为0900~1500小时。结果。在放置在栅栏上的大鼠身上,悬浮在栅格表面下1厘米的水中,不仅三唑仑,而且氟硝西潘和苯巴比妥都能缩短睡眠潜伏期。氟硝西潘和苯巴比妥均能有效增加木屑和格子上大鼠的总非快速眼动睡眠时间,且两药对格子上大鼠的影响均大于木屑上。每小时非快速眼动睡眠时间的测量有助于研究这三种催眠药的作用高峰时间和持续时间。苯巴比妥显示放置在格子上的大鼠的总REM睡眠时间减少,尽管三唑仑和氟硝西潘都没有影响。结论。本失眠模型不仅可作为睡眠障碍模型,还可用于检测催眠药的催眠效应和维持睡眠效应,包括非快速眼动睡眠和快速眼动睡眠。
Rationale. New sleep disturbance model in rats is useful for estimating the characteristics of some hypnotics. Objectives. The present study was undertaken to investigate the utility of a sleep disturbance model by placing rats on a grid suspended over water using three kinds of hypnotics, that is, short-acting benzodiazepine (triazolam), intermediate-acting benzodiazepine (flunitrazepam) and long-acting barbiturate (phenobarbital). Methods. Electrodes for measurement of EEG and EMG were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-REM and REM sleep were measured from 0900 to 1500 hours. Results. In rats placed on the grid suspended over water up to 1 cm under the grid surface, not only triazolam but also flunitrazepam and phenobarbital caused a shortening of sleep latency. Both flunitrazepam and phenobarbital were effective in increasing of total non-REM sleep time in rats placed on sawdust or the grid, and the effects of both drugs in rats placed on the grid were larger than those in rats placed on sawdust. Measurement of the hourly non-REM sleep time was useful for investigating the peak time and duration of effect of the three hypnotics. Phenobarbital showed a decrease in total REM sleep time in rats placed on the grid, although both triazolam and flunitrazepam were without effect. Conclusions. The present insomnia model can be used as a sleep disturbance model for testing not only the sleep-inducing effects but also the sleep-maintaining effects including non-REM sleep and REM sleep of hypnotics.