吗啡戒断后条件性位置厌恶大鼠伏隔核壳区CREB表达  

CREB EXPRESSION IN THE SHELL OF ACCUMBENS NUCLEUS OF RATS WITH CONDITIONED PLACE AVERSION INDUCED BY MORPHINE WITHDRAWAL

作　　者：李秀梅[1] 李文强 乔振 宋秀花 李毅 

机构地区：[1]安徽省泗县人民医院血透室,泗县234300 [2]河南省精神卫生中心河南省生物精神病学重点实验室,新乡453002 [3]华中科技大学同济医学院附属精神卫生中心,武汉430022

出　　处：《中国药物依赖性杂志》2013年第3期191-196,共6页Chinese Journal of Drug Dependence

基　　金：国家自然科学基金(30800364);武汉市青年科技晨光计划(200850731391);国家临床重点专科建设项目

摘　　要：目的:探讨慢性吗啡依赖大鼠纳洛酮催瘾戒断后条件性位置厌恶(conditioned place aversion,CPA)建立、消退和重建过程中,伏隔核壳区(shell of accumbens nucleus,AcbSH)内cAMP反应元件结合蛋白(cyclic-3’,5’adenosine monophosphate response element binding protein,CREB)蛋白表达的适应性变化。方法:(1)连续6 d半每天2次吗啡腹腔注射(10 mg.kg-1.次-1),纳洛酮一次腹腔注射催瘾(0.3 mg.kg-1)搭配训练箱建立CPA,相继对其进行连续7 d(12次,15 min.次-1)消退,然后再经吗啡点燃和纳洛酮催瘾注射搭配训练箱重建CPA。(2)采用免疫组化的方法,于CPA建立后、消退后和重建后不同时间点,检测大鼠AcbSH内CREB的表达情况。结果:(1)慢性吗啡腹腔注射纳洛酮一次腹腔注射催瘾搭配训练箱成功建立CPA大鼠模型,且可被消退和重建。(2)CPA建立后,AcbSH内磷酸化CREB(p-CREB,Ser-133)较对照组表达显著增强(P<0.05);CPA经消退后,p-CREB表达亦相应地显著降低(P<0.01);CPA重建后,p-CREB显著性高表达(P<0.01)。结论:(1)AcbSH可能是慢性吗啡注射纳洛酮催瘾后CPA的重要解剖基础;(2)提示AcbSH内CREB介导的可塑性变化是中枢的情绪状态和强化效应重要的分子机制。Objective：To explore the changes of cAMP response element binding protein（CREB） in the shell of accumbens nucleus（AcbSH） at the post-formation,post-extinction and post reinstatement of morphine withdrawal-induced conditioned place aversion（CPA） in rats.Methods：（1） Using an unbiased conditioning paradigm,we treated rats with morphine hydrochloride,10 mg.kg-1,intraperitoneally（ip）,twice per day for 6.5 days,subsequently naloxone（0.3 mg.kg-1 ip） was injected on day 6 to precipitate withdrawal,which is paired with the compartment to develop CPA.Then,the rats exhibiting CPA were received 12 extinction trials by being exposed to the two compartments with free exploration.On day 13,the rats with the extinguished CPA were treated with a priming injection of morphine,10 mg.kg-1,ip,followed by naloxone,0.3 mg.kg-1,ip,to reinstate the CPA.（2） Immunohistochemistry technique was used to measure the expression of phosphorylated CREB（p CREB,Ser-133） in AcbSH.Results：（1） The used experimental procedure could develop obvious CPA in rats,and the CPA could be extincted and reinstated,respectively.（2） At the post-formation of the CPA,the p-CREB expression was significantly increased in the AcbSH（P 0.05）,was significantly decreased at the post-extinction of the CPA（P 0.01）,and was increased at the post-reinstatement of the CPA（P 0.01）,respectively,compared with that in controls.Conclusion：（1） The AcbSH may be one of anatomic substrates implicating in the CPA induced by morphine withdrawal in rats.（2） The neuroadaptation mediated by CREB may be one of molecular mechanisms of the emotional state and reinforcements in the AcbSH.

关 键 词：条件性位置厌恶 成瘾 消退 重建 

分 类 号：R722.12[医药卫生—儿科]