莨菪类生物碱与吗啡并用对小鼠吗啡成瘾性的影响(英文)

Belladonna alkaloid combined with morphine for morphine-addicted mice

背景:莨菪碱类药物改善微循环和作为中药麻醉剂已在国内临床上广泛应用,但莨菪类生物碱抗吗啡成瘾作用的动物实验缺乏深入报道。目的:观察莨菪类生物碱与吗啡合用对抗吗啡致小鼠依赖性的作用,以期为开发防治阿片类物质成瘾的莨菪类药物提供实验学依据。设计:以实验动物为研究对象的随机对照实验。单位:一所大学医学院的生理学实验室。材料:本实验于2004-06/2004-08在河北工程学院医学部生理学实验室完成。选择健康雄性昆明小鼠50只,2月龄,体质量(20±2)g,由河北医科大学实验动物中心提供,清洁级。方法:依据吗啡成瘾动物的依赖性评价指标,选择痛阈和纳络酮跳台反应作为观察项目。将50只小鼠随机分为5组,即对照组、吗啡组、东莨菪碱组、山莨菪碱组和阿托品组,每组10只。分别于第1天至第7天每天用热板法观察腹腔注射生理盐水、吗啡及莨菪类生物碱合并吗啡后1h的痛阈。并于末次(第7天)给药后6h,腹腔注射纳络酮5mg/kg催促,观察30min内小鼠跳跃次数。主要观察指标:①吗啡成瘾小鼠的痛阈;②吗啡成瘾小鼠的跳跃次数和跳跃动物数(率)。结果:与对照组比较,吗啡组小鼠的痛阈明显下降(P<0.05或P<0.01),跳跃次数和跳跃动物率明显增加。东莨菪碱与吗啡合用7d后,明显提高吗啡依赖小鼠的痛阈(P<0.01)。

BACKGROUND:Belladonna drugs have been widely used in clinic in our country to improve microcirculation,or as a herbal anesthetic drug.However,there are few re ports regarding the animal experiments on belladonna alkaloid against morphine a ddiction further OBJECTIVE:To observe the effects of belladonna alkaloid combined with morphine on morphine(Mor) addicted mice so as to provide an experimental basis for deve lopment of belladonna to morphine addiction. DESIGN:A completely randomized controlled study based on the experimental an imals. SETTING:Laboratory of physiology of a medical college. MATERIALS:The study was performed at the Laboratory of Physiology of Medical D epartment of Hebei Engineering College from June 2004 to August 2004.Fifty 2 mo nth old male healthy Kunming mice of clean grade with a body mass of(20±2)g wer e obtained from Experimental Animal Centre of Hebei Medical University. METHODS:According to evaluation index of dependence in Morphine addicted anim als,we chose pain threshold and naloxone urged jumping response as items to obs erve.Fifty mice were randomly divided into 5 groups with 10 mice each,which were the control group (saline),the morphine group,the scopolamine(Sco) group,the an isodamine(Ani),atropine(Atr) group.The corresponding drugs or saline was adminis tered by intraperitoneal(i.p.) injection once a day for 7 days.The pain threshol d at 1 hour after i.p.injection of drugs was observed from day 1 to day 7 by hot plate method.Mice were given i.p. injection of naloxone (Nal, 5 mg/kg ) 6 hour s after the last injection.The jumping times within 30 minutes were observed to evaluate the formation of the Morphine addiction. MAIN OUTCOME MEASURES:①Pain threshold of mice in each group;②jumping times a nd the number of the mice that jumped (jumping rate) in Nal urged mice. RESULTS:The pain threshold of the mice in Morphine group was decreased signifi cantly,and the jumping times and jumping rate were obviously increased compared with that of the control group(P< 0.05 or P< 0.01). The co administration of Sco Mor mixtures for 7 days significantly increased the pain threshold of Mor dependent mice(P< 0.01) and markedly decreased the j umping times and the jumping rate(P< 0.05).Atr Mor and Ani Mor had a weak effe ct on the elevation of the pain threshold of Mor dependent mice,but had strong effects on the decrease of the jumping times and the jumping rate(P< 0.01). CONCLUSION:Belladonna alkaloids all could antagonize Mor dependence in mice a t different degrees,which provide an important experimental evidence to develop belladonna drugs for preventing opium addiction.