海洛因成瘾易感性的前额叶皮质多巴胺D2受体及多巴胺转运体机制

Dopamine D2 receptor and transptor mechanism in the prefrontal cortex of the susceptibility to heroin addiction

目的 建立大鼠海洛因成瘾易感性差异模型,探讨其可能的前额叶皮质D2受体（D2R）及多巴胺转运体（DAT）机制.方法 130只雄性SD大鼠随机抽取30只为生理盐水对照组（SC）,其余100只大鼠为海洛因处理组,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）,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30min、戒断第1,3,7,14天PFC区D2R和DAT蛋白表达进行动态检测.结果 ①高、低偏爱组和对照组之间D2R蛋白灰度值在成瘾期[（149.33±2.51）,（135.83±1.78）,（99.33±2.84）]及戒断第1[（141.83±2.50）,（131.67±1.87）,（99.17±3.61）]、3[（132.83±2.40）,（122.00±2.67）,（100.33±4.26）]、7[（125.67±2.22）,（113.17±2.81）,（98.33±3.25）]、14天[（116.86±1.94）,（108.63±2.31）,（98.17±3.82）]的差异均有统计学意义（F值分别为114.59,65.45,26.50,31.88,11.33,P＜0.05）,两两比较显示,在各检测时点高、低CPP组均高于对照组（P＜0.05）,而高CPP组均高于低CPP组（P＜0.05）;②高、低偏爱组和对照组之间前额叶皮质DAT蛋白灰度值在成瘾期及戒断第1,3天的差异均有统计学意义（F值分别为89.17,34.68,12.03,P＜0.05）,两两比较显示,高、低CPP组均高于对照组（P＜0.05）,至戒断第7天和戒断第14天3组间的差异无统计学意义（P＞0.05）;高、低偏爱组之间在所有检测时点DAT蛋白灰度值差异均无统计学意义（P＞0.05）.结论 海洛因慢性处理后,大鼠PFC区D2R和DAT均出现适应性下调;PFC区低D2R可能与海洛因成瘾的高易感性与有关;海洛因成瘾易感性与PFC区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 addiction,and to explore the possible dopamine D2 receptor （D2R） and dopamine transptor （DAT） 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 detectedwith immunohistochemical method in PFC at 30 minutes and on the 1st,3rd,7th, 14th days after the last injection（149.33 ±2.51 vs 135.83 ±1.78 vs99.33 ±2.84,141.83 ±2.50 vs 131.67 ± 1.87 vs99.17 ±3.61,132.83 ±2.40 vs 122.00 ±2.67 vs 100.33 ±4.26,125.67 ±2.22 vs 113.17 ±2.81 vs 98.33 ±3.25,116.86 ± 1.94 vs 108.63 ± 2.31 vs 98.17 ± 3.82 , respectively, P〈0.05）. The D2R protein expressions of HP rats were significantly lower than those of the LP and control group rats （P 〈 0. 05）, and those of LP rat were than lower than those ferent among three groups on addiction phase and 1st,3rd days after the last injection of heroin respectively, respectively （P 〈 0. 05）. The DAT protein expressions of HP and LP rats were significantly lower than those of controlgroup rats （P〈 0. 05）. At all testing time-points, the DAT protein expressions had no significant difference betweenHP and LP group（P〉0. 05）. Conclusion D2R and DAT of the rats show appears down-regulation in the PFC after chronic heroin exposure. Different individuals have different D2R sensitivity or receptor levels ,and lower D2R related to the high susceptibility to heroin. Susceptibility to heroin addiction may not be directly related to the expression of DAT.