盐酸戊乙奎醚对大鼠曲马多依赖及相关脑区c—fos、△FosB及M5受体表达的影响  

Effect of penehyclidine hydrochloride on tramadol dependence and c-fos, △ FosB and Ms receptor expression in relevant brain regions in rats

作　　者：昌睿杰[1] 秦成名[1] 陈凯[1] 詹佳[1] 陈畅[1] 王焱林[1] 

机构地区：[1]武汉大学中南医院麻醉科,430071

出　　处：《中华麻醉学杂志》2011年第9期1083-1086,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨盐酸戊乙奎醚对大鼠曲马多依赖及相关脑区c—fos、△FosB及M5受体表达的影响。方法雄性成年sD大鼠30只，体重180—220g，采用随机数字表法，将其随机分为3组（n=10）：对照组（c组）、曲马多依赖组（T组）和盐酸戊乙奎醚组（P组）。T组和P组连续7d交替皮下注射曲马多10mg／kg（9：00）或生理盐水（16：00），诱导大鼠曲马多条件性位置偏爱效应。实验第8天停用曲马多，P组腹腔注射盐酸戊乙奎醚1．5mg／kg，C组及T组腹腔注射等量生理盐水，30rain后行条件性位置偏爱实验，记录大鼠伴药区停留时间。条件性位置偏爱实验结束后处死大鼠，取出大脑，分离相关脑区（中脑腹侧被盖区、前额叶皮层、伏隔核），采用Westernblot法检测c．fos、△F0sB蛋白的表达，RT-PCR法检测M5受体mRNA的表达水平。结果与C组比较，T组伴药区停留时间延长，c2fos、△FosB蛋白和M5受体mRNA表达上调，P组M5受体mRNA和△FosB蛋白表达下调（P〈0．05或0．01），伴药区停留时间和c—fos蛋白表达水平差异无统计学意义（P〉0．05）；与T组比较，P组伴药区停留时间缩短，c—fos和△FosB蛋白和M5受体mRNA表达下调（P〈0．01）。结论盐酸戊乙奎醚可减轻大鼠曲马多依赖，其机制可能与下调相关脑区c—fos、△FosB蛋白和M，受体基因表达有关。Objective To investigate the effect of penehyclidine hydrochloride （PHCD） on tramadol dependence and c-fos, △FosB and M5 receptor expression in relevant brain regions in rats. Methods Thirty male adult SD rats weighing 180-220 g were randomly assigned to 3 groups （n = 10 each）： control group （group C）, tramadol dependence group （group T） and PHCD group （group P）. Tramadol dependence was induced by subcutaneous 10 mg/kg once a day for 7 consecutive days in groups T and P. PHCD 1.5 mg/kg was injected intraperitoneally on day 8 in group P, while in groups C and T the equal volume of normal saline was injected intraperitone- ally instead of PHCD. The rats underwent conditioned place perference test at 30 min after intraperitoneal injection. The time spent in drug-paired side （gray area） was recorded. The rats were sacrificed after the conditioned place perference testand the brain was removed. The relevant brain regions （ventral tegmental area, prefrontal cortex , nucleus accumbens ）were separated for determination of c-fos, △ FosB expression by Western blot and M5 receptor mRNA expression by RT-PCR. Results Compared with group C, the time spent in the drug-paired side （gray area） was significantly prolonged, and c-fos, △ FosB and M5 receptor mRNA expressions were up-regulated in group T, △FosB and M5 receptor mRNA expressions were down-regulated in group P （P 〈 0.05 or 0.01）. There was no significant difference in time spent in the drug-paired side （gray area） and c-fos expression between groups C and P（P 〉 0.05）. Compared with group T, the time spent in the drug-paired side （gray area） was significantly shortened, and c-los, △FosB and M5 receptor mRNA expressions were down-regulated in group P （P 〈 0.01 ）. Conclusion PHCD can significantly inhibit tramadol dependence by down-regulating c-fos, △ FosB and M5 receptor expression in relevant brain regions.

关 键 词：胆碱能拮抗剂 曲马朵 物质相关性障碍 原癌基因蛋白质C-FOS 受体 胆碱能 

分 类 号：R965[医药卫生—药理学]