盐酸戊乙奎醚对曲马多依赖大鼠相关脑区cAMP、p-CREB及D_2受体的影响  

Effect of Penehyclidine Hydrochloride on the Content of cAMP and the Expression of p-CREB and D_2 Receptor in the Relevant Brain Regions in Tramadol Dependent Rats

作　　者：彭俊敏 昌睿杰[2] 陈凯[2] 詹佳[2] 陈畅[2] 张宗泽[2] 王焱林[2] 

机构地区：[1]湖南省株洲市331医院麻醉科,湖南株洲412002 [2]武汉大学中南医院麻醉科,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2011年第6期757-760,共4页Medical Journal of Wuhan University

摘　　要：目的:观察盐酸戊乙奎醚(PHC)对曲马多依赖大鼠相关脑区cAMP、p-CREB及D2受体的影响。方法:雄性SD大鼠30只,随机分为3组(n=10):对照组(C组)、曲马多依赖组(T组)和盐酸戊乙奎醚治疗组(P组)。连续7d皮下注射曲马多,诱导大鼠曲马多依赖条件性位置偏爱效应(CPP)。第8天P组腹腔注射PHC;C组及T组腹腔注射等体积的生理盐水。30min后各组大鼠行CPP测试。实验结束后处死大鼠,分离相关脑区(中脑腹侧被盖区、前额叶皮层、伏隔核)。检测cAMP含量、p-CREB的蛋白表达和D2受体的mRNA水平。结果:与T组比较,P组灰区停留时间缩短;相关脑区中cAMP、p-CREB含量显著降低(P<0.01)、D2的mRNA含量明显升高(P<0.01)。与C组比较,T组灰区停留时间延长,相关脑区中cAMP、p-CREB含量显著增高(P<0.05或P<0.01)、D2受体的mRNA含量显著降低(P<0.01)。结论:盐酸戊乙奎醚能抑制曲马多依赖大鼠条件性位置偏爱的表达,该效应可能通过降低相关脑区cAMP含量,抑制p-CREB蛋白表达,上调D2受体mRNA等起作用。Objective： To investigate the effect of penehyclidine hydrochloride（PHC） on the content of cAMP and expression of phosphorylation of cyclic AMP response element binding protein（p-CREB） and D2 receptor of the relevant brain regions in tramadol dependent rats.Methods： Thirty male SD rats were randomly and equally assigned to three groups as normal saline control group（C group）,tramadol dependent group（T group）,and PHC treatment groups（P group）.The tramadol conditioned place preference（CPP） was induced by alternate subcutaneous injection of tramadol for 7 days in rats.On the 8th day,the rats received CPP test.The rats of P group were treated with PHC prior to the CPP test,whereas the rats were treated with saline in T and C group.The rats were sacrificed after CPP test,relevant brain regions including ventral tegmental area,prefrontal cortex,and nucleus accumbens were harvested.The content of cAMP were determined by ELISA.Western blotting was used to measure the expression of p-CREB.PCR was used to detected the mRNA level of D2 receptor.Results： Compared with T group,the time spent in the drug-paired side（gray area） was shortened in P group（P0.01）,the cAMP and p-CREB contents were significantly decreased（P0.01）,and D2 receptor mRNA levels were significantly increased（P0.01） in P group.Compared with C group,the cAMP and p-CREB contents in T group were significantly increased（P0.05 or P0.01） and D2 receptor mRNA levels decreased significantly（P0.01）.Conclusion： PHC could significantly inhibit the expression of CPP on tramdol dependent rats,and this effect might be related to the reduction of cAMP content,inhibition of the expression of p-CREB,and up-regulation of D2 receptor mRNA in relevant brain regions.

关 键 词：胆碱能拮抗剂 曲马多依赖 中脑腹侧被盖区 伏隔核 前额叶皮层 CAMP P-CREB D2受体 

分 类 号：R964[医药卫生—药理学]