吗啡条件性位置偏爱易感性差异的内侧前额皮质多巴胺D2受体和多巴胺转运体机制

The role of dopamine D2 receptor and transporter in the different susceptibility of morphine-induced conditioned place preference in rats

目的通过研究高低吗啡条件性位置偏爱（CPP）易感性大鼠内侧前额皮质区（mPFC）的多巴胺D1受体（D，R）和多巴胺转运体（DAT）表达差异，以探讨吗啡精神依赖易感性差异的D2R和DAT机制。方法160只雄性大鼠随机分为实验组130只和对照组30只。建立大鼠吗啡CPP动物模型，根据吗啡处理后CPP值将大鼠分为高、中、低偏爱组。其中高、低偏爱组大鼠进入以下研究。分别于末次注射后3h、72h和第14天各处死高偏爱组、低偏爱组和对照组各8只，利用组织原位杂交技术检测mPFC脑区D：RmRNA和DAT mRNA的表达。结果①高偏爱组、低偏爱组和对照组的CPP预测试值差异无显著性（P〉0．05）；CPP训练后，末次注射后3h、72h和第14天，高偏爱组的CPP值与预测试的差值均高于低偏爱组（P〈0．01）。②mPFC的D2R mRNA灰度值：末次用药后3h、72h和第14天，高偏爱组[（125．43±2．90）-（142．92±3．32）]、低偏爱组[（122．25±2．20）～（136．67±5．39）]，两两比较高偏爱组的D2R mRNA灰度值均高于低偏爱组（P〈0．01）；③DAT mRNA灰度值：末次注射后3h，高偏爱组灰度值（157．00±3．55）高于低偏爱组（150．69±3．12），差异有显著性（t=7．564，P=0．000）；在末次注射后72h，高偏爱组灰度值（145．15±3．69）高于低偏爱组灰度值（138．84±3．99），差异有显著性（P〈0．01）；在末次注射后第14天，高偏爱组、低偏爱组及对照组的mPFC区DATmRNA灰度值差异无显著性（P〉0．05）。结论 mPFC的D2R mRNA表达低下可能与吗啡高易感性有关；mPFC的DAT mRNA表达低下可能与吗啡高易感性有关。

Objective To investigate the expression of dopamine D2 receptor（ D2R） and dopamine transporter（DAT） located in the medial prefrontal contex（mPFC） in high and low CPP rats, thus to unveil the possible mechanism lead to the different CPP susceptibility. Methods 160 male Sprague-Dawley rats were randomly assigned into experiment group （n = 130） and control group （n = 30）. The experiment group were re-classified into two groups according to the numerical value of the CPP（ Conditioned place preference） ：high preference group（ HP group） and low preference group（ LP group）. Further, according tn the executed time-points after the last administration, each the HP and LP group was classified into 3-hour group （3H） ,72-hour group（JD3 ） and 14-day group （JD14） respectively. At the time of 3 hours, 72 hours and 14 days after the final injection, rats were scarified and cardio-perfused, and the brains were removed and sliced up coronarily. The mRNA levels of D2R and DAT in mPFC were estimated with in situ hybridization. Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups （P 〉 0.05 ）, however, the test scores of the CPP minus the time stayed at pretest natural preference in the HP group was significantly higher than the LP group（P 〈 0.01 ）. In 3H, J3 D and J I4D group, the expression of D2 R mRNA in HP group （125.43 ± 2.90 - 142.92 ± 3.32 ） were lower that of in LP group （ 122.25 ± 2.20 - 136.67 ± 5.39） , and the difference between the HP and LP group was signif- icant（P 〈 0.01 ）. In 3H and J3D, the expression of DAT mRNA in HP group （157.00 ±3.55 - 145.15 ± 3.69 ） were significantly lower than that of in LP group （ 150.69 ± 3.12 - 138.84 ± 3.99） （P 〈 0.01 ）. In J14D, there were no difference between 3 groups in mPFC （P 〉 0. 05 ）. Conclusions It can be inferred that D2 R and DAT maybe correlated closely and underlie the different susceptibility to morphine induced CPP.