海洛因成瘾易感性与腹侧被盖区多巴胺D2受体及多巴胺转运体的关系  

The study on the association of dopamine D2 receptor and transporter in ventral tegmental area(VTA) with the susceptibility to heroin addiction in Sprague-Dawley rats

作　　者：王传升[1] 谌红献[2] 张瑞玲[1] 郝伟[2] 

机构地区：[1]新乡医学院第二附属医院,新乡453002 [2]中南大学湘雅二医院精神卫生研究所

出　　处：《中国神经精神疾病杂志》2010年第8期463-467,共5页Chinese Journal of Nervous and Mental Diseases

基　　金：国家重点基础研究发展计划(973)课题(编号:2003C515400);国家自然科学基金资助项目(编号:30370522)

摘　　要：目的建立大鼠海洛因成瘾易感性差异模型,探讨其可能的腹侧被盖区(VTA)D2受体(D2R)及多巴胺转运体(DAT)机制。方法 130只雄性SD大鼠随机分为海洛因成瘾组(n=100)和对照组(n=30)接受7d的条件性位置偏爱(CPP)训练和2d的测评,期间两组分别给予海洛因和生理盐水注射处理。此后,成瘾组根据海洛因诱导的CPP强度挑选出高CPP组(n=30)和低CPP组(n=30)。各组大鼠再随机分为5组,在接受末次处理后分别于成瘾期、戒断第1、3、7、14天检测VTA区D2R和DAT的蛋白表达,蛋白检测采用免疫组织化学法。结果与对照组相比,高CPP组和低CPP组大鼠在成瘾期VTA区D2R和DAT蛋白表达均下降(P<0.05);戒断后第1、3、7、14天D2R及戒断第1、3天DAT仍低于对照组(P<0.05),而戒断第7、14天高、低CPP组分别与对照组的DAT差异均已无统计学意义(P<0.05);在所有检测时点,高CPP组VTA区D2R下调均比低CPP组大鼠更为明显(P<0.05),而两组的DAT表达差异均无统计学意义(P>0.05)。结论海洛因慢性处理可诱导大鼠VTA区D2R和DAT下调;而海洛因成瘾易感性可能与VTA区低D2R有关,但未见与DAT相关。Objective To establish the rat model of different susceptibility of heroin addiction,and to explore the possible D2 receptor（D2R） and dopamine transptor（DAT） mechanism leading to the different susceptibility.Methods One hundred thirty male SD rats were randomly assigned into heroin exposure group（n=100） and saline control group（n=30）.Animals then received 7 d consecutive injection of either heroin or saline and underwent conditioned place preference（CPP）training.Heroin exposure group rats were further classified into two subgroups according to the numerical value of the CPP-Pre（the testing score minus that of the pretest）：high preference group（HP）（n=30） and low preference group（LP）（n=30）.The D2R and DAT protein expressions in VTA were detected using immunohistochemical method at 30 minutes and on the 1st,3rd,7th,14th days after the last injection of heroin.Results ① D2R protein expression in VTA of heroin exposure group were significantly lower than those of saline control group during the addiction phase;D2R on the 1st,3rd,7th,14th days and DAT on the 1st,3rd days after withdrawal were significantly lower in the heroin exposure group than in the control group（P0.05）.DAT on the 7th,14th days were no significant difference between heroin exposure group and control group（P0.05）.② At all testing time-points,the D2R protein expression in HP rats were significantly lower than those in LP rats（P0.05）.There was no significant difference in the DAT protein expression between HP and LP group（P0.05）.Conclusions ① Chronic heroin exposure can induce down-regulation of D2R and DAT in the VTA of rats.② The high susceptibility to heroin may be associated with lower expression of D2R,but not with the expression of DAT.

关 键 词：海洛因依赖 多巴胺D2受体 多巴胺转运体 腹侧被盖区 易感性 

分 类 号：R749.61[医药卫生—神经病学与精神病学]