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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 observe the effects of penehyclidine hydrochloride (PHC) on cAMP, p-CREB and D2 receptors in the brain regions of tramadol dependent rats. Methods: Thirty male SD rats were randomly divided into 3 groups (n = 10): control group (C), tramadol dependence group (T group) and penehyclidine hydrochloride treatment group (P group). Tramadol was injected subcutaneously for 7 days, and tramadol was induced to rely on conditional place preference (CPP). On the 8th day, the rats in group P were injected intraperitoneally with PHC. Rats in group C and group T were injected intraperitoneally with equal volume of normal saline. 30min after the rats in each group CPP test. After the experiment, the rats were sacrificed and the relevant brain regions (mesencephalic ventral tegmental area, prefrontal cortex, nucleus accumbens) separated. The content of cAMP, the protein expression of p-CREB and the mRNA level of D2 receptor were detected. Results: Compared with group T, the residence time in gray zone of group P was shortened. The contents of cAMP and p-CREB were significantly decreased in related brain regions (P <0.01), and the mRNA levels of D2 were significantly increased (P <0.01). Compared with group C, the residence time of gray zone in group T was prolonged, and the contents of cAMP and p-CREB in the relevant brain regions were significantly increased (P <0.05 or P <0.01), while the mRNA levels of D2 receptors were significantly decreased (P <0.01). CONCLUSION: Penehyclidine hydrochloride can inhibit the conditioned place preference of tramadol dependence in rats, which may play a role in decreasing cAMP content, inhibiting the expression of p-CREB protein and up-regulating D2 receptor mRNA in the relevant brain regions.