吗啡依赖及戒断对大鼠脑源性神经营养因子表达的影响(英文)

Heroin-dependence and detoxification in the expression of brain-derived neurotrophic factor in rat

背景:阿片类药物多次用药可引起脑内有关神经部位出现形态及功能的适应性变化,这些适应性变化是导致药物渴求和戒断后复吸的重要神经生物学基础,但其确切的分子机制目前尚不清楚。目的:研究吗啡依赖形成及戒断对大鼠脑源性神经营养因子表达的影响,以期为脑源性神经营养因子参与阿片类药物依赖及戒断反应提供实验学依据。设计:以实验动物为观察对象的随机设计,对照研究。单位:一所医科大学医院的心理卫生中心。材料:实验于2004-03/2004-07在重庆医科大学药学系药理实验室完成。选择近交清洁级Sprague-Dawley大鼠30只,均为雄性,体质量200～250g,购自解放军第三军医大学实验动物中心。按随机数字法将其分为空白对照组、吗啡依赖组、盐酸纳洛酮处理戒断组,每组10只。方法:采用剂量递增法皮下注射吗啡建立大鼠吗啡依赖模型,然后对戒断组大鼠皮下注射2mg/kg的盐酸纳络酮激发戒断症状。空白对照组大鼠按同等剂量给予生理盐水。分别对建立模型的各组大鼠进行生物学和行为学的观察。应用免疫组化和地高辛标记寡核苷酸探针原位杂交技术检测3组大鼠不同脑区脑源性神经营养因子的表达水平。主要观察指标:①各组大鼠脑内脑源性神经营养因子蛋白、脑源性神经营养因子mRNA平均光密度的比较;②各组大鼠戒断症状评定比较?

BACKGROUND:Multiple applications of opium medicines can induce the accommodati ve changes of morphology and function in some intracerebral nerve positions.Thes e accommodative changes are important neurobiological bases inducing drug desir e and re addiction after detoxification.However,the actual molecular mechanism is unclear at present. OBJECTIVE:To investigate the impacts of the generation of heroin dependence a nd detoxification on brain derived neurotrophic factor(BDNF) in rat to provide a laboratorial gist for the participation of BDNS in heroin dependence and deto xification. DESIGN:A randomized controlled study by employing experimental animals as subj ects SETTING:Mental health center of a medical university affiliated hospital MATERIALS:The study was conducted in the Laboratory of Pharmacology, Faculty o f Pharmacology,Chongqing Medical University between March 2004 and July 2004.Tot ally 30 inbreeding clean male SD rats with a bodymass between 200 g and 250 g we re obtained from the Experimental Animal Center of the Third Military Medical Un iversity of Chinese PLA.Rats were randomly divided into blank control group(cont rol group),heroin dependent group(heroin group),and naloxone detoxification gro up(naloxone group) with 10 rats each. METHODS:Morphine was subcutaneously injected into the rat with dose increasin g method to establish heroin dependence rat model.Rats of naloxone group receiv ed subcutaneously injection of 2 mg/kg of naloxone to excite abstinent symptoms. The same dose of normal saline(NS) was injected in rats of control group.Model r ats of each group were observed biologically and behaviorally.BDNF expression at different brain zone of rats in three different groups was tested with immunohi stochemistry and digoxin labeled oligonucleoide probe in situ hybridization tec hnique. MAIN OUTCOME MEASURES:①The comparison of BDNF protein,BDNFmRNA mean optical d ensity in the brain of rats among each group;②Comparison of the evaluation of a bstinent symptoms in rats of each group. RESULTS:In the heroin group,the relative content of BDNF protein was higher in frontal lobe cortex,locus caeruleus and hippocampus than that of the control gr oup(P< 0.05);BDNFmRNA relative content was higher in frontal lobe cortex than th at of the control group(P< 0.05). In naloxone group,BDNF and its mRNA relative c ontents in frontal lobe cortex, locus caeruleus and hippocampus were higher than that of heroin group and control group(P< 0.05). CONCLUSION:Chronic administration of heroin could affect BDNF protein and its mRNA expressions in the corresponding brain areas of the rats,which suggests tha t the change of BDNF expression participates in heroin dependence and detoxific ation.