CAJ | 학술논문

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180～220 g,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1.5 mg/kg,C组及T组腹腔注射等量生理盐水,30 min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Western blot法检测c-fos、△FosB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,c-fos、△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蛋白和地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M5受体基因表达有关.
목적 탐토염산무을규미대대서곡마다의뢰급상관뇌구c-fos、△FosB급M5수체표체적영향.방법 웅성성년SD대서30지,체중180～220 g,채용수궤수자표법,장기수궤분위3조(n=10):대조조(C조)、곡마다의뢰조(T조)화염산무을규미조(P조).T조화P조련속7d교체피하주사곡마다10mg/kg(9:00)혹생리염수(16:00),유도대서곡마다조건성위치편애효응.실험제8천정용곡마다,P조복강주사염산무을규미1.5 mg/kg,C조급T조복강주사등량생리염수,30 min후행조건성위치편애실험,기록대서반약구정류시간.조건성위치편애실험결속후처사대서,취출대뇌,분리상관뇌구(중뇌복측피개구、전액협피층、복격핵),채용Western blot법검측c-fos、△FosB단백적표체,RT-PCR법검측M5수체mRNA적표체수평.결과 여C조비교,T조반약구정류시간연장,c-fos、△FosB단백화M5수체mRNA표체상조,P조M5수체mRNA화△FosB단백표체하조(P＜0.05혹0.01),반약구정류시간화c-fos단백표체수평차이무통계학의의(P＞0.05)；여T조비교,P조반약구정류시간축단,c-fos화△FosB단백화지M5수체mRNA표체하조(P＜0.01).결론 염산무을규미가감경대서곡마다의뢰,기궤제가능여하조상관뇌구c-fos、△FosB단백화M5수체기인표체유관.
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 intraperitoneally 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 Ms 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-fos,△ 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.