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Wistar-Kyoto大鼠和Sprague-Dawley大鼠中的抗抑郁药与快速眼动睡眠

Antidepressants and REM sleep in Wistar-Kyoto and Sprague-Dawley rats.

作者信息

Ivarsson Magnus, Paterson Louise M, Hutson Peter H

机构信息

Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.

出版信息

Eur J Pharmacol. 2005 Oct 17;522(1-3):63-71. doi: 10.1016/j.ejphar.2005.08.050. Epub 2005 Oct 11.

Abstract

Compared to other rat strains, the Wistar-Kyoto rats show increased amount of REM sleep, one of the characteristic sleep changes observed in depressed patients. The aims of this study were firstly to validate a simple sleep stage discriminator and then compare the effect of antidepressants on suppression of rapid eye movement (REM) sleep in Wistar-Kyoto rats and an outbred rat strain (Sprague-Dawley). Rats were implanted with telemetry transmitters with electroencephalogram/electromyogram electrodes. Following recovery, the animals were orally dosed at light onset with either desipramine (20 mg/kg), fluoxetine (10 mg/kg), citalopram (10 or 40 mg/kg) or vehicle in a cross-over design. Every 12-s epoch was automatically scored as WAKE, NREM or REM sleep. Results confirm that Wistar-Kyoto rats show increased amount of REM sleep and decreased REM latency compared with Sprague-Dawley rats. All antidepressants significantly suppressed REM sleep in Sprague-Dawley rats, but only the high dose of citalopram suppressed REM sleep in Wistar-Kyoto rats. These findings suggest that the enhanced REM activity in Wistar-Kyoto rats is less sensitive to the effect of antidepressants and therefore does not provide any additional predictive validity for assessing antidepressant efficacy.

摘要

与其他大鼠品系相比,Wistar-Kyoto大鼠表现出快速眼动睡眠量增加,这是抑郁症患者观察到的特征性睡眠变化之一。本研究的目的首先是验证一种简单的睡眠阶段鉴别器,然后比较抗抑郁药对Wistar-Kyoto大鼠和远交系大鼠(Sprague-Dawley)快速眼动(REM)睡眠抑制的影响。给大鼠植入带有脑电图/肌电图电极的遥测发射器。恢复后,在光照开始时以交叉设计给动物口服地昔帕明(20 mg/kg)、氟西汀(10 mg/kg)、西酞普兰(10或40 mg/kg)或赋形剂。每12秒的时间段自动分为清醒、非快速眼动或快速眼动睡眠。结果证实,与Sprague-Dawley大鼠相比,Wistar-Kyoto大鼠的快速眼动睡眠量增加,快速眼动潜伏期缩短。所有抗抑郁药均显著抑制Sprague-Dawley大鼠的快速眼动睡眠,但只有高剂量的西酞普兰抑制Wistar-Kyoto大鼠的快速眼动睡眠。这些发现表明,Wistar-Kyoto大鼠增强的快速眼动活动对抗抑郁药的作用不太敏感,因此在评估抗抑郁药疗效方面没有提供任何额外的预测效度。

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