吗啡依赖与戒断大鼠脑组织μ阿片受体的变化(英文)

Changes of μ-opioid receptor in the brain tissues of morphine-dependent and abstinent rats

背景:内源性阿片肽-阿片受体系统的改变是阿片类药物成瘾的一个重要机制。在离体条件下,给予μ阿片受体拮抗剂或激动剂可以调节阿片受体水平。但不同的实验结果差别很大。目的:用光学放射自显影术对吗啡依赖与戒断大鼠脑组织μ阿片受体进行定位和定量研究。设计:完全随机分组实验研究。地点和对象:实验在第二军医大学长征医院麻醉科完成,对象为雄性SD大鼠30只,体质量180～220g,由第二军医大学动物实验中心提供。干预:30只SD大鼠随机分为吗啡依赖组、吗啡戒断组和生理盐水对照组,每组10只。依赖组和戒断组大鼠以腹腔注射吗啡的方法建立吗啡依赖模型,戒断组在成瘾后腹腔注射纳洛酮5mg/kg诱导戒断24h,对照组注射生理盐水。主要观察指标:大鼠不同脑区μ阿片受体特异性结合密度。结果:依赖组大鼠与对照组大鼠相比,额叶皮质、海马、纹状体、丘脑、下丘脑的μ受体特异性结合密度发生非常显著下降(t=11.54,17.82,15.80,8.35,13.78,P<0.01),下降幅度分别为22%,49%,21%,28%,39%;戒断组大鼠与吗啡依赖组比较,额叶皮质、海马、纹状体、丘脑、下丘脑的μ受体特异性结合密度发生了显著的上调(t=3.72,7.77,5.84,3.06,11.24,P<0.01),上调幅度分别为10%,38%,12%,13%,58%。但除下丘脑外(t=1.64,P>0.05)。

BACKGROUND:The alteration of endogenous opioid peptide system is one of the im portant mechanisms for opioid dependence.μ opioid receptor antagonist or activ ator can regulate opioid receptor in vitro,but the results from the animal exper iment vary greatly. OBJECTIVE:To study the localization and quantitative changes of μ-opioid rec eptor in the brain tissues of morphine-dependent and abstinent rats. DESIGN:A completely randomized controlled experimental study. SETTING and MATERIALS:The experiment was conducted in the Department of Anaest hesiology,Changzheng Hospital,Second Military Medical University using 30 male S D rats provided by the Experimental Animal Center,Second Military Medical Univer sity. INTERVENTIONS:Thirty SD rats were divided randomly into 3 groups(n=10).Intrape ritoneal injection with morphine was given to the rats in morphine-dependent gr oup and abstinent group to produce morphine-dependent models,and 3 hours after the model establishment,the rats in the abstinent group were injected with nalox one(5 mg/kg) to induce the withdrawal syndromes.The rats in the control group re ceived only injection with saline.All rats were sacrificed by decapitation 24 ho urs after the last injection of morphine,and the coronal sections of discrete br ain regions(namely the frontal cortex,hippocampus,striatum,thalamus,and hypothal amus) were prepared. MAIN OUTCOME MEASURES:The localization and density of μ-opioid receptor in t he specified brain regions of rats in all the 3 groups were measured by autoradi ography. RESULTS:In morphine dependent group,the density of μ-opioid receptor in the frontal cortex,hippocampus,striatum,thalamus,and hypothalamus were significantly lowered by 22%,49%,21% and 28%,respectively(t=11.54,17.82,15.80,8.35,13.78 ,respectively,P< 0.01) in comparison with the control group.In morphine abstinen t group,the densities of μ opioid receptor in those brain regions were signifi cantly higher by 10%,38%,12%,13%,and 58% respectively(t=3.72,7.77,5.84,3.0 6,11.24,respectively,P< 0.01) than those in dependent group,but remained lower i n then frontal cortex,hippocampus,striatum,thalamus that those in the control gr oup(t=6.76,11.73,10.19,5.46,respectively,P< 0.01) with the exception of that in the hypothalamus(t=1.64,P >0.05). CONCLUSION:Morphine dependence can lower the level of μ-opioid receptor in r at brain,which is difficult to correct through short-term morphine abstinence b y naloxone and can be one of the neurobiological mechanisms of opioid dependence and abstinence.