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。
Objective To investigate the expression of dopamine D2 receptors (D2 R ) and dopamine transptors (DAT) located in the medial prefrontal contex (mPFC) in high and low conditioned place preference ( susceptibilities. Methods CPP ) rats, and to unveil the possible mechanism leading to different CPP 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 reclassified 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 (J3 d), 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 D2 R 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 12 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 D2 R and DAT may be correlated closely and underlie the different susceptibilities to morphine induced CPP.
出处
《中南大学学报(医学版)》
CAS
CSCD
北大核心
2008年第9期784-789,共6页
Journal of Central South University :Medical Science
基金
国家自然科学基金项目(30500180)
国家973项目(2003CB515403)
河南省科技基金项目(2004-5)~~
关键词
吗啡
精神依赖
条件性位置偏爱
易感性
多巴胺D2受体
多巴胺转运体
morphine
psychological dependence
conditioned place preference
susceptibility
dopamine D2 receptor
dopamine transportor