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1. 北京协和医院核医学科
2. 江苏省原子医学研究所核医学国家重点实验室
3. 北京协和医院核医学科,北京,100730
4. ,无锡,214063
纸质出版日期:2006-01-01
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[1]林岩松,丁时禹,陈正平,王博诚,张满达,王世真.吗啡戒断大鼠脑多巴胺转运蛋白及D2受体的研究[J].核技术,2006(01):55-58.
LIN Yansong1 DING Shiyu2 CHEN Zhengping2 WANG Bocheng1 ZHANG Manda2 WANG Shizhen1 1. Exploration of central dopamine transporter and D2 receptor in morphine abstinent rats[J]. Nuclear techniques, 2006, (1): 55-58.
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
125I-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.
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