大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

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

目的探讨吗啡条件性位置偏爱（CPP）不同易感性的大鼠脑伏隔核多巴胺D2受体（D2R）和多巴胺转运体（DAT）水平。方法将160只雄性Sprague—Dawley大鼠随机抽取30只作为对照组，余130只为吗啡组。对吗啡组在预测试后建立吗啡CPP模型。根据CPP值[以末次CPP测评时大鼠在伴药侧（大鼠注射吗啡后放入该侧，吗啡剂量从5mg·kg^-1·次^-1开始逐渐增加，第10天为50mg·kg^-1·次^-1）的停留时间减去预测试在该侧停留的时间]将吗啡组大鼠按比例分为高（26只）、中（78只）、低偏爱组（26只），其中高、低偏爱组（每组大鼠死亡各2只）分别于吗啡末次注射（对照组注射同体积生理盐水）后3h、3d和14d分别处死大鼠（每组各8只），用原位杂交法检测伏隔核D：R和DAT的灰度值（阳性区域的强弱与灰度值呈反比），并与对照组比较。结果（1）预测试3组CPP值的差异无统计学意义（P〉0．05）；但在吗啡注射后3h、戒断后3d和14d，高偏爱组CPP值[分别为（507±108）s、（524±113）s、（483±60）s]均长于低偏爱组[分别为（100±74）s、（166±86）s、（149±89）s；P：0．000]和对照组[分别为（97±111）s、（39±26）s、（-4．9±140．1）s；P=0．000]。（2）上述各时点高偏爱组D：RmRNA灰度值（131±3、122±5、119±5）均高于低偏爱组（125±4、117±8、114±5）和对照组（111±6、107±7、106±3；P〈0．01）；高偏爱组DATmRNA灰度值（161±5、143±4、134±6）亦高于低偏爱组（156±5、139±3、130±4）和对照组（120±4、126±7、129±4；P〈0．01）。结论大鼠吗啡CPP易感性高可能与伏隔核的D2R及DAT表达低下有关。

Objective To explore the possible role of the expression of dopamine D2 receptor （D2R） and dopamine transporter （DAT） located in the nucleur accumben （Nac） in rats with different CPP susceptibility. Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group （n = 130） and control group （n = 30 ）. The experiment rats were re-classified into three groups according to the numerical value of the CPP （ conditioned place preference） , high preference group （ HP group, n = 26 ） , moderate preference group（ n = 78 ） and low preference group （ LP group, n = 26）. At the time of 3 hours, 72 hours and 14 days after the final injection, rats in each group were scarified, and the mRNA levels of D2 R and DAT in Nac 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. 470） , however, the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group（ P 〈 0. 01 ）. In each time-point, the expression of D2R mRNA in HP group, were lower that in LP group [ （ 131 ± 3, 122 ± 5, 119 ± 5） and （ 125 ± 4, 117 ± 8, 114 ± 5 ）, P 〈 0. 01 ]. In each time-point, the expression of DAT mRNA in HP group, were significantly lower than that in LP group [ （161 ±5, 143 ±4, 134 ±6） and （156 ±5, 139 ± 3, 130 ± 4）, P 〈 0. 01 ]. Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the different susceptibility to morphine induced CPP.