长期使用氯米帕明对大鼠睡眠/觉醒及食欲素的影响

目的探讨长期注射氯米帕明对大鼠睡眠/觉醒周期和脑内食欲素系统的影响。方法成年雄性SD大鼠分为生理盐水组和氯米帕明组,每组8只。每12小时腹腔注射1次生理盐水或氯米帕明。于第六周行96h睡眠描记。结束后取额叶皮层、海马和下丘脑行RT-PCR。结果大鼠的运动觉醒和快速眼球运动睡眠的时间显著减少,安静觉醒和慢波睡眠时间显著增加(P<0.01)。氯米帕明显著地抑制了额叶皮层、海马和下丘脑食欲素前体和食欲素2受体mRNA的表达(P<0.05,P<0.01)。结论氯米帕明在剥夺快速眼球运动睡眠的同时减少了运动觉醒,其抑制食欲素前体和食欲素2受体mRNA表达,但是不影响食欲素1受体mRNA的表达。

Objective To characterize sleep/waking cycles and orexin system in rats to be treated long time with clomipramine.Methods Sixteen adult male Sprague-Dawley（SD） rats were divided into saline group and clomipramine group.Intraperitoneal injection was operated each 12 hours.Sleep recording was done on 96 hours at sixth week.After the end of recording,the frontal cortex,hippocampus and hypothalamus was collected and RT-PCR was performed.Results ①The duration of active wake and REM sleep were significantly decreased in rats those received clomipramine;while the quiet wake and slow wave sleep duration were significantly increased（P0.01）.②The expression of prepro-orexin and OX2R mRNA were significantly decreased by administration of clomipramine in the frontal cortex,hippocampus and hypothalamus（P0.05,P0.01）.Conclusions Treatment of long time clomipramine significantly suppressed active wake and REM sleep,while increased quiet wake.Consistently,this treatment also suppresses the expression of prepro-orexin mRNA and OX2R mRNA,which promote the active wake.But clomipramine did not affect the expression of OX1R mRNA.