东莨菪碱对吗啡诱发CPP重现大鼠海马p-CREB及c-Fos表达的影响

Effect of scopolamine on expression of p-CREB,c-Fos in rat hippocampus in recurrence of Conditioned place preference induced by morphine

目的:探讨东莨菪碱对吗啡诱发条件位置性偏爱激活大鼠海马(hippocampus,Hip)cAMP反应元件结合蛋白(phos-pho-cAMP response element binding protein,p-CREB)和c-Fos表达的变化。方法:以吗啡剂量递增法6d建立大鼠条件位置性偏爱(conditioned place preference,CPP)模型,生理盐水替代吗啡训练大鼠10d,使形成的CPP逐渐消退,小剂量吗啡激发已消退的CPP。采用免疫组化技术检测不同剂量东莨菪碱对吗啡诱发CPP重现时大鼠海马p-CREB和c-Fos表达的变化。结果:东莨菪碱可抑制吗啡点燃诱发大鼠CPP重现行为;并可减少吗啡诱发的CPP重现时大鼠海马p-CREB和c-Fos的表达。结论:东莨菪碱对小剂量吗啡诱发吗啡依赖大鼠CPP重现行为的抑制作用可能与其抑制大鼠海马p-CREB和c-Fos蛋白表达有关。

OBJECtIVE To dectect the effect of scopolamine on expression of phospho-cAMP response element binding pro tein （p-CREB） and c-Fos in rat hippocampus（Hip） in recurrence of conditioned place preference（CPP） induced by morphine. METHODS Morphzine was administered by subcutaneously injection（sc）at gradually increasing dose（from 10 mg·kg ^-1 to 60 mg· kg^-1 ）for 6 days to establish morphine CPP. From d7, the rats were administered saline instead of morphine for 10 days to induce CPP extinction. The rats were given a single priming injection of morphine （4 mg·kg^-1 ） to reinstate the morphine CPP, some rats were treated by intraperitoneal injection（ip） scopolamine （1,2,3 mg·kg^-1 ） prior to priminging injection of morphine. The expression of p-CREB and c-Fos in Hip were assayed with immunohistochemistry method in the phase of recurrence of CPP. RESULTS （1） After priming injection of morphine 4 mg·kg^-1 , the time spent on the drug paired side was significantly reduced because of the treatment with scopolamine, compared with morphine group（P〈0. 05）; （2） Compared to morphine group, scopolamine could decrease the expression of p-CREB and c-Fos of Hip in rats （P〈0. 05）. CONCLUSION The effect of scopolamine inhibited morphine-induced CPP recurrence probably relates to its inhibitory effect on p-CREB and c-Fos expression of Hip in rats.