SD大鼠海洛因CPP易感性差异的伏隔核壳区D_2受体及DAT机制  

Dopamine D_2 Receptor and Transptor in the Shell of Accumbens Nucleus of Heroin-induced Conditioned Place Preference in Sprague-dawley Rats

作　　者：王传升[1] 谌红献[1] 郝伟[1] 

机构地区：[1]中南大学湘雅二医院精神卫生研究所,湖南长沙410011

出　　处：《中国临床心理学杂志》2009年第5期566-569,587,共5页Chinese Journal of Clinical Psychology

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

摘　　要：目的:建立大鼠海洛因成瘾易感性差异的条件性位置偏爱模型,检测海洛因CPP易感性差异大鼠伏隔核壳区(AcbSH)D2受体(dopamine D2 receptor,D2R)及多巴胺转运体(dopamine transportor,DAT)蛋白表达的动态变化,探讨海洛因精神依赖易感性差异可能机制。方法:130只雄性SD大鼠随机抽取30为生理盐水对照组(SC),其余100只大鼠为海洛因处理组进行条件性位置偏爱(CPP)训练,海洛因处理组根据海洛因诱导的CPP强度不同再分为高CPP组(HP)和低CPP组(LP),各占总数的30%,利用免疫组化方法对高、低偏爱组及生理盐水对照组大鼠末次海洛因注射后30分钟、戒断第1、3、7、14天AcbSHD2R和DAT蛋白表达进行检测。结果:①海洛因处理后大鼠AcbSH区D2R和DAT蛋白表达均显著下降,而在戒断后逐渐回升;②海洛因高偏爱组大鼠在所有检测时点AcbSH区D2R下调比低偏爱组大鼠更为明显;③海洛因高偏爱组大鼠各脑区所有检测时点DAT表达与低偏爱组大鼠均无明显差别。结论:①海洛因慢性处理后,大鼠AcbSH区D2R和DAT均出现适应性下调;②不同个体D2R敏感性或受体水平存在差异,低D2R可能与海洛因成瘾的高易感性与有关;③未发现不同易感性的大鼠DAT蛋白水平存在差异,海洛因成瘾易感性与DAT的表达可能没有直接的相关性。Objective： To establish the rats model of different susceptibility of heroin-induced conditioned place preference （CPP） and investigate the time-point dopamine D2 receptor （D2R） and dopamine transptor （DAT） protrin expression in the shell of accumbens nucleus （AcbSH） in high and low susceptibility to heroin-induced CPP rats, and to explore the possible mechanism leading to the different susceptibility. Methods： 130 male SD rats were carried out CPP training, and the rats were randomly assigned into heroin exposure group （n=100） and saline control group （SC, n=30）. Heroin exposure group were re-classified into two groups according to the numerical value of the CPP-Pre （the testing score minus that of the pretest）： high preference group（HP group） and low preference group（LP group）, each accounting for 30% of the total rats. The D2R and DAT protein expression of high and low preference group and saline control group rats were detected with immunohistochemical method in AcbSH at 30 minutes and on the 1st, 3ird, 7th, 14th days after the last injection of heroin respectively. Results： ①D2R and DAT protein expression of heroin exposure group rats were significantly lower than those of saline control group on addiction phase in AcbSH, and increased gradually after withdrawal. ②At all testing time-points, the D2R protein expressions of HP rats were significantly lower than those of the LP rats. ③At all testing time-points, the DAT protein expressions had no significant difference between HP and LP group. Conclusion： ①D2R and DAT of the rats show appears down-regulation in the AcbSH after chronic heroin exposure. ② Different individuals have different D2R sensitivity or receptor levels, and lower D2R related to the high susceptibility to heroin. ③Susceptibility to heroin addiction may not be directly related to the expression of DAT.

关 键 词：海洛因 多巴胺D2受体 多巴胺转运体 条件性位置偏爱 易感性 

分 类 号：R395.2[哲学宗教—心理学]