褪黑素抗大鼠吗啡奖赏效应的表达与脑内CREB及其磷酸化  

MELATONIN REVERSES THE EXPRESSION OF MORPHINE-INDUCED REWARDING EFFECT AND INVOLVEMENT OF CREB AND PHOSPHORYLATION IN BRAIN

作　　者：韩静[1] 许盈[1] 魏义明[1] 黄静[1] 俞昌喜[1] 

机构地区：[1]福建医科大学药学院药理学系,福州350004

出　　处：《中国药物依赖性杂志》2008年第6期414-418,共5页Chinese Journal of Drug Dependence

基　　金：福建省重点高校建设科研基金重点项目(XZ04008);福建省自然科学基金项目(C0410018)资助

摘　　要：目的:观察褪黑素(melatonin,Mel)对大鼠吗啡诱导的条件性位置偏爱(CPP)效应表达的影响及此过程中脑内cAMP反应元件结合蛋白(CREB)及其磷酸化的变化。方法:(1)大鼠连续6 d给予吗啡(sc,5 mg.kg-1/d)建立CPP模型,于CPP测试前20 min ip Mel(50和25 mg.kg-1),观察Mel对大鼠吗啡诱导的CPP效应表达的影响。(2)大鼠同上建立吗啡CPP模型,d7上、下午,d8上午ip Mel 50 mg.kg-1,共3次,最后一次ip后6 h,采用免疫组化结合计算机图像处理技术测定脑内伏隔核、海马内CREB及磷酸化CREB(p-CREB)的免疫阳性反应强度。结果:Mel 50 mg.kg-1可显著翻转大鼠吗啡诱导的CPP评分升高(P<0.01),同时显著降低吗啡诱导的大鼠伏隔核、海马内p-CREB的上调(P<0.01)。结论:Mel抑制大鼠吗啡奖赏效应的表达,此作用可能与其抑制吗啡诱导的伏隔核、海马内p-CREB蛋白水平上调有关。Objective ： To observe the effect of melatonin （Mel） on the expression of morphine - induced conditioned place preference （CPP） in rats and changes of cAMP response element binding protein（CREB） and CREB in the brain during this process. Methods： （1） The CPP was established by morphine （ sc, 5 mg · kg^-1, once daily for 6 consecutive days） in rats. Mel （50 and 25 mg · kg^-1 ） was administrated 20 min before the CPP testing .to observe the effect of melatonin on the expression of morphine -induced CPP. （2） The CPP in rats was established as described above. From d7, Mel （50 mg· kg^-1 ip） was administrated twice daily （in the morning and the afternoon）, and on d8 morning, ip Mel, totally 3 times. 6 h after the last administration, the immunoreactivities of CREB and p - CREB in the nucleus accumbens （NAc） and the hippocampus （Hip） were detected by immunohistochemistry analysis. Results：Melatonin 50 mg · kg^-1 significantly reversed morphine- induced increase in CPP scores in rats （P 〈 0.01 ） ; and decreased the upregulation of p - CREB protein level in the NAc and the Hip induced by morphine during this process （P 〈 0. 01 ）. Conclusion：Melatonin may reverse the expression of morphine - induced rewarding effect, and this action may be relevant to its ability to decrease the upregulation of p -CREB protein level in the NAc and the Hip induced by morphine.

关 键 词：条件性位置偏爱 褪黑素 吗啡 CREB 磷酸化CREB 伏隔核 海马 

分 类 号：R285[医药卫生—中药学] R722.12[医药卫生—中医学]