慢性吗啡依赖大鼠条件性位置厌恶模型脑腹侧被盖区蛋白激酶A的表达变化  

Changes of Protein Kinase A Expression in Ventral Tegmental Area of Rats with Conditioned Place Aversion Induced by Morphine Withdrawal

作　　者：李毅 宋秀花[2] 李文强[2] 张景丹[2] 张瑞岭[2] 石玉中[1] 郝伟[3] 

机构地区：[1]华中科技大学同济医学院附属精神卫生中心(武汉市精神卫生中心),武汉430022 [2]新乡医学院第二附属医院,河南省生物精神病学重点实验室,新乡453002 [3]中南大学湘雅二院精神卫生研究所,长沙410011

出　　处：《华中科技大学学报（医学版）》2012年第3期337-340,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30800364);武汉市青年科技晨光计划资助项目(No.200850731391)

摘　　要：目的分析慢性吗啡依赖大鼠条件性位置厌恶(conditioned place aversion,CPA)模型脑腹侧被盖区(ventraltegmental area,VTA)蛋白激酶A(protein kinase A,PKA)蛋白表达的适应性变化,探讨阿片依赖戒断后厌恶动机形成的生物学基础。方法①将72只雄性Sprague-Dawley(SD)大鼠分为研究组(慢性吗啡注射+纳洛酮催瘾组,MN组),对照组(慢性吗啡注射+生理盐水组,MS组;慢性生理盐水注射+纳洛酮组,SN组),每组24只。采用慢性吗啡腹腔注射(10mg/kg,Bid,ip.)后予1次纳洛酮(0.3mg/kg)催瘾注射,同时与条件性位置训练箱搭配使用建立大鼠CPA模型。②在CPA建立前后,采用免疫组织化学方法检测VTA内PKA蛋白表达情况。结果 CPA建立前,MN组PKA蛋白表达水平与对照组(MS组和SN组)比较差异无统计学意义(F=0.013,P=0.987)。CPA建立后,3组PKA蛋白表达水平比较差异有统计学意义(F=9.853,P=0.018),MN组灰度值(127.500±3.536)显著低于MS组[(140.500±3.697),P<0.05]和SN组[(138.000±2.944),P<0.05]。结论①VTA内PKA蛋白高表达,可能是CPA建立的神经机制之一。②VTA内PKA的适应性变化可能是物质依赖戒断后CPA相关神经可塑性变化的重要分子基础之一。Objective To explore neurobiological mechanisms of the morphine withdrawal-induced aversion,and the changes of protein kinase A expression in ventral tegmental area（VTA）of conditioned place aversion（CPA）model rats.Methods ① All 72 male SD rats were divided into three groups：model group（MN group）,and control groups（MS group and SN group）.In MN group,morphine was injected,6.5 days,10 mg/kg,intraperitoneally（ip.）,twice every day,and naloxone,0.3 mg/kg,ip.,along with CPA training,to develop the CPA model.The MS group was administrated equivalent volume of morphine and saline.Also the SN group was injected with equivalent volume of saline and naloxone;② During the development of CPA,the expression of protein kinase A in the VTA of rats was detected by using immunohistochemistry.Results Before establishment of CPA model,PKA expression in the VTA had no significant difference among the three groups（F=0.013,P=0.987）.After establishment of CPA model,there was significant difference in the PKA expression among the three groups（F=9.853,P=0.018）.The average gray intensity in MN group（127.500±3.536）was apparently decreased as compared with that in MS group（140.500±3.697,P0.05）,and SN group（138.000±2.944,P0.05）.Conclusion The expression of protein kinase A in the VTA of rats probably is one of key molecular mechanisms contributing to the development of CPA.The neuroadaptation mediated by protein kinase A may be one of important molecular underpinnings of CPA.

关 键 词：条件性位置厌恶 蛋白激酶A 腹侧被盖区 戒断 

分 类 号：R749.611[医药卫生—神经病学与精神病学]