吗啡戒断大鼠脑多巴胺转运蛋白及D2受体的研究  

Exploration of central dopamine transporter and D2 receptor in morphine abstinent rats

作　　者：林岩松[1] 丁时禹[2] 陈正平[2] 王博诚[1] 张满达[2] 王世真[1] 

机构地区：[1]北京协和医院核医学科,北京100730 [2]江苏省原子医学研究所核医学国家重点实验室,无锡214063

出　　处：《核技术》2006年第1期55-58,共4页Nuclear Techniques

基　　金：国家自然基金资助(项目批准号30100044)项目

摘　　要：采用多巴胺转运蛋白(DAT)示踪剂125I-甲基-3β-(4-碘苯基)托烷-2β-羧酸酯(β-CIT)及D2受体示踪剂125I-左旋-3-碘-2-羟基-6-甲氧基-N[(1-乙基-2-吡咯烷)甲基]苯酰胺(IBZM)探讨吗啡戒断前、后大鼠脑突触前、后多巴胺(DA)系统的变化。吗啡戒断1、2、3天组大鼠(各10只)分别于连续给予吗啡(20mg/kg)8天后停止给予吗啡1、2、3天再进行实验;吗啡(20mg/kg)组及生理盐水对照组大鼠各12只;对照组大鼠只给予腹腔注射0.3mL生理盐水,共计8天。将吗啡组、戒断1、2、3天组及生理盐水对照组大鼠各进一步随机平均分为两组,分别用于125I-IBZM、125I-β-CIT脑内分布研究。结果:(1)吗啡戒断组大鼠自戒断第2天开始出现明显的腹泻症状,同时还伴有叩齿及寒战等症状出现。(2)在20mg/kg吗啡及戒断组的125I-β-CIT脑内分布中,吗啡组在纹状体(ST)、伏隔核(NAC)的分布明显高于戒断1、2、3天组和对照组(P<0.05),在额叶(FC)、海马(HIP)的分布也高于戒断组及对照组(P<0.05)。戒断1、2、3天组在ST、NAC及HIP的分布与对照组比较差异无显著性(P>0.05)。(3)125I-IBZM在吗啡依赖及戒断组的脑内分布显示:吗啡组在ST、NAC的分布明显低于戒断1、2、3天组和对照组(P<0.05);在HIP及皮层的分布也低于对照组及戒断各组(P<0.05)。戒断1、2、3天组在ST、NAC的125I-IBZM分布增加逐渐增高,其中戒断各组在ST的分布均低于对照组(P<0.05);在NAC戒断1天组仍低于对照组(P<0.05),而戒断2、3天组125I-IBZM在NAC的分布与对照组比较差异无显著性(P>0.05)。由此可得出结论:吗啡戒断组大鼠出现了明显的戒断症状。在吗啡依赖中ST、NAC及HIP等的DAT出现了上调,D2受体则出现一种下调的低敏状态,吗啡戒断使这种增高DA能的活动及DAT回落并趋于正常范围,并使NAC及ST下调的D2受体逐渐回升。The experiment was designed to investigate the variation of DAT and D2 receptor in morphine administered and 1,2,3 day abstinent rats. Morphine exposure was induced by repeated morphine （i.p.） treatment for 8 days. Conditioned place preference test was conducted to evaluate the drug seeking behaviour and morphine dependence of rats with morphine exposure. Biodistribution of the imaging agents ^125I-β-CIT and ^125I-IBZM was used to evaluate the central DAT and D2 receptor during morphine exposure and 1,2,3 day＇s abstinence. Results reveal the following facts. （1） The morphine abstinent rats showed diarrhea and body-shake 1 day after morphine withdrawal. （2） For morphine group, 125^I-β-CIT %ID/g in ST and NAC was higher than that of the 1,2,3 day＇s abstinent rats and control （P〈0.05）. No difference was found between 1,2,3 day＇s abstinent group and control group （P〉0.05）. （3） ^125I-IBZM %ID/g in ST, NAC and HIP in morphine rats were lower than those of the abstinent and control rats （P〈0.05）. The ^125I-IBZM %ID/g in ST and NAC gradually increased with the abstinent days. While in ST the %ID/g among the abstinent rats was all lower than that of the control rats, in NAC the %ID/g was still lower in 1 day＇s abstinent rats （P〈0.05）, and no difference in 2 and 3 day＇s abstinent rats was observed in comparison with the control （P〉0.05）, indicating the reduction of hyper-activated DAT and the increase of down-regulatory D2 receptor induced by morphine during morphine withdrawal. Our results confirmed that the dopamine system, especially DAT and D2 receptor in mesolimbic and meso-striatum pathway, has been implicated in morphine treatment. The rewarding properties of morphine and the somatic expression of morphine abstinence were related to changes in mesolimbic and meso-striatum dopaminergic activity.

关 键 词：药物依赖 吗啡 多巴胺转运蛋白 D2受体 ^125I-B-CIT ^125I-IBZM 

分 类 号：R749[医药卫生—神经病学与精神病学]