慢性吗啡依赖大鼠条件性位置厌恶模型杏仁中央核蛋白激酶A表达变化  

Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats

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

机构地区：[1]新乡医学院第二附属医院,河南新乡453002 [2]青岛市精神卫生中心,湖北武汉430022 [3]武汉市精神卫生中心,山东青岛266034

出　　处：《中国应用生理学杂志》2012年第4期328-331,389,共4页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(30800364);武汉市青年科技晨光计划资助项目(200850731391)

摘　　要：目的:分析慢性吗啡依赖大鼠纳洛酮催瘾戒断条件性位置厌恶(CPA)建立前后、消退后及重建后,与成瘾密切相关的脑区杏仁中央核(CeA)内蛋白激酶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将雄性SD大鼠分为实验组(慢性吗啡注射+纳洛酮催瘾组,MN),对照组(慢性吗啡注射+生理盐水催瘾组,MS),慢性生理盐水注射+纳洛酮催瘾组,SN),每组24只。采用慢性吗啡注射(10 mg/kg,BID,ip)后给予一次纳洛酮(0.3 mg/kg)催瘾注射(同时与条件性位置训练箱搭配)建立大鼠CPA模型。②在CPA建立前后、消退后及重建后,采用免疫组织化学方法检测CeA内PKA蛋白表达情况。结果:MN组在CPA建立前后、消退后及重建后CeA内PKA的蛋白表达出现适应性变化(P<0.05),建立后(Day7,134.43±4.481,P<0.05),消退后(Day13,141.01±3.360,P<0.01)及重建后(Day14,137.18±40.330,P<0.05)PKA蛋白表达水平均低于建立前(Day5,124.48±6.722)。而MS组(P>0.05)和SN组(P>0.05)在CPA的各个时间点PKA的蛋白表达变化差异均无显著性。结论:①CeA内PKA蛋白的低表达导致的厌恶的中枢状态,可能是CPA建立的关键的神经机制。②CeA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。Objective： To explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleis （CeA） 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 group （MS group and SN group）. MN group was injected with morphine, 6.5 days, 10 mg/kg, intraperitoneaUy （ip）, twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion 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 process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA. Results： In the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA（ P 〈 0.05）. Protein kinase A expressions after establishment（ Day7,134.43 ± 4. 481, P 〈 0.05）, and after extinction（ Dayl3, 141.01 ± 3.360, P 〈 0. 01 ）, and after reinstatement （Dayl4,137.18 ± 40.330, P 〈 0.05）were also lower than those before the establishment of the CPA（ DayS, 124.48 ±6. 722）. However, PKA expressions were not significantly different both in MS group（ P 〉 0.05） and SN group （ P 〉 0.05）. Conclusion： （1）Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. （20The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.

关 键 词：条件性位置厌恶 蛋白激酶A 杏仁中央核 免疫组化 

分 类 号：R749[医药卫生—神经病学与精神病学]