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中枢NO cGMP系统对大鼠吗啡戒断症状的影响

杨彦玲 刘秀平 邱学才 李静 刘晓红 徐丽 卢景芬

【摘要】目的:观察中枢NO-cGMP系统对大鼠吗啡戒断症状的影响。方法:用皮下递增注射吗啡法建立吗啡依赖模型,腹腔注射纳洛酮催瘾。侧脑室注射(i.c.v.)不同药物,观察对大鼠叩齿、扭体、湿狗样抖动、舔阴茎、逃逸、体重丢失等吗啡戒断症状的影响。结果:微量侧脑室注射(i.c.v.)NO的供体硝普钠(SNP)、NO的前体L-精氨酸(L-Arg)、环磷酸鸟苷(cGMP)以增加脑内NO的释放,激活鸟苷酸环化酶(GC),提高脑内cGMP水平,结果使吗啡戒断症状加重;相反,微量注射NO合酶(NOS)抑制剂NG-硝基-L精氨酸(LNNA)及鸟苷酸环化酶(GC)抑制剂甲基兰(MB),使脑内NO生成减少,降低NO对GC的激活作用,脑内cGMP生成减少,则可使大鼠吗啡戒断症状减轻。结论:NO-cGMP系统在产生吗啡戒断反应中具有重要作用。
【关键词】NO-cGMP系统 硝普钠  吗啡戒断症状

Effect of Central NO-cGMP System on Morphine Withdrawal Symptoms in Morphine Dependent Rats

Yang Yanling Liu Xiuping Qiu Xuecai et al.
(Department of physiology, Beijing Medical University, Beijing, CHINA 100083)

【Abstract】Objective: To observe the effect of central NO-cGMP system on morphine withdrawal symptoms in morphine dependent rats. Method: A physical morphine dependent model in rats was established by subcutaneous injection of morphine in gradually increasing doses (from 5mg/kg to 50mg/kg in five days). After intraperitoneal injection of naloxone (0.5mg/kg), withdrawal symptoms including teeth chattering, writhing, wet shakes, penile licking, escape attempts and weight loss were scored to assess the effects of various drugs by intracerebroventricular microinjection(icv) on them. Results: Morphine wiehdrawal symptoms were aggravated due to the release of NO and the activation of guanosine cyclase (GC) by icv of the donor of NO (sodium nitroprusside), the precursor of NO (L-Arg) and cGMP. In contrast, those symptoms were relieved by microinjection of the inhibitor of NO synthetase (NG-nitro-L-Arginine, NNLA) and the inhibitor of GC (methylene blue, MB). Conclusion: NO-cGMP system plays an important role in the development of morphine withdrawal symptoms in rats.
【Key words】NO-cGMP system sodium nitroprusside morphine withdrawal symptoms

  NO是一种新发现的神经递质和信使分子,是细胞间信息交换的重要载体[1]。硝普钠(sodium nitroprusside,SNP)在体内不需要酶促可以自发性释放NO[2]。L-Arg是NO 的前体物质,可在一氧化氮合酶(NO syntha

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