【摘要】 目的:通过研究高低吗啡条件性位置偏爱(conditioned place preference,CPP)易感性大鼠内侧前额皮质区(mPFC)的多巴胺D2受体和多巴胺转运体差异,以探讨吗啡精神依赖易感性差异的多巴胺D2受体和多巴胺转运体机制。方法:160只雄性大鼠随机分为实验组(n=130)和对照组(n=30)。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3 h,72 h和第14天处死高偏爱组、低偏爱组和对照组各8只大鼠,利用组织原位杂交技术检测mPFC脑区多巴胺D2受体(dopamine D2recepter,D2R)mRNA和多巴胺转运体(dopamine transporter,DAT)mRNA的表达。结果:高偏爱组、低偏爱组和对照组的CPP预测试值无统计学差异(P=0.470);CPP训练后,末次注射后3 h、末次注射后72 h和第14天,高偏爱组的CPP值与预测试值的差值均高于低偏爱组(P=0.000)。mPFC的D2RmRNA灰度值:末次用药后3 h,72 h和第14天,高偏爱组(125.43±2.90~142.92±3.32)均高于低偏爱组(122.25±2.20~136.67±5.39)(P=0.000)。DATmRNA灰度值:末次注射后3 h,高偏爱组(157.00±3.55)高于低偏爱组(150.69±3.12)(P=0.000);在末次注射后72 h,高偏爱组(145.15±3.69)高于低偏爱组(138.84±3.99)(P=0.000);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灰度值无统计学差异(P=0.458)。结论:mPFC的D2RmRNA和DATmRNA低表达可能与吗啡高易感性有关。更多还原

【Abstract】 Objective To investigate the expression of dopamine D2 receptors(D2R) and dopamine transptors(DAT) located in the medial prefrontal contex(mPFC) in high and low conditioned place preference(CPP) rats,and to unveil the possible mechanism leading to different CPP susceptibilities.Methods One hundred and sixty male Sprague-Dawley rats were randomly assigned into an experiment group(n=130) and a control group(n=30).The experiment group was re-classified into 2 groups according to CPP values:high preference group(HP group) and low preference group(LP group).According to the execution time-points after the last administration,the HP and LP group was classified into a 3-hour group(3 h),a 72-hour group(J3d),and a 14-day group(J14d),respectively.At 3 hours,72 hours,and 14 days after the final injection,rats were killed and cardio-perfused,and the brains were removed and sliced up coronarily.The mRNA levels of D2R and DAT in mPFC were determined with in situ hybridization.Results There were no significant differences of pretest scores staying at the non-preference chamber among the groups(P=0.470).However,the test scores of the CPP time stayed at pretest natural preference in the HP group were significantly higher than those of the LP group(P=0.000).In 3h,J3d,and J14d groups,the expressions of D2R mRNA in the HP group(125.43±2.90～142.92±3.32) were lower than those of LP group(122.25±2.20～136.67±5.39)(P=0.000).In 3h and J3d,the expressions of DAT mRNA in the HP group(157.00±3.55～145.15±3.69) were significantly lower than those of the LP group(150.69±3.12～138.84±3.99)(P=0.000).In J14d,there were no differences among 3 groups in mPFC(P=0.458).Conclusion D2R and DAT may be correlated closely and underlie the different susceptibilities to morphine induced CPP.更多还原