吗啡依赖及戒断对大鼠强啡肽原mRNA表达的影响  

Effect of morphine dependence and abstinence on the expression of pro-dynorphin mRNA in Sprague-Dawley rats

作　　者：万兴旺[1] 黄矛[2] 何雅琴[1] 李万亥[3] 由振东[4] 路长林[4] 

机构地区：[1]第二军医大学东方肝胆外科医院国际合作信号转导研究中心,上海200438 [2]第二军医大学基础医学部新药评价中心,上海200438 [3]第二军医大学药学院药理学教研室,上海200438 [4]第二军医大学基础医学部神经生物学教研室,上海200438

出　　处：《中华精神科杂志》2003年第2期94-97,共4页Chinese Journal of Psychiatry

基　　金：中国人民解放军新药研究基金资助项目 (96 0 2 )

摘　　要：目的　研究吗啡依赖形成及戒断对大鼠强啡肽原mRNA表达的影响。方法　将 18只Sprague Dawley雄性大鼠随机分为吗啡依赖组、吗啡戒断组和空白对照组 ,每组 6只。采用皮下注射吗啡建立大鼠吗啡依赖模型 ,初剂量为 10mg/kg ,以后每天增加 5mg/kg ,3次 /d ,连续 6天。应用放射性3 2 磷标记的三磷酸脱氧胞苷掺入标记探针法进行Northern印迹杂交技术检测三组大鼠强啡肽原mRNA的表达水平。结果　 (1)连续 6天给予吗啡 ,吗啡依赖组大鼠下丘脑 (2 3 88± 1 6 2 )、纹状体(19 87± 2 0 3)及脊髓 (13 36± 1 4 6 )的强啡肽原mRNA相对含量分别低于对照组 (分别为 34 36±1 4 6、31 2 4± 2 83和 2 7 6 0± 2 89;均P <0 0 1) ,海马 (2 9 6 7± 3 2 3)强啡肽原mRNA相对含量高于对照组 (2 5 87± 1 74 ,P <0 0 5 ) ;(2 )给予纳洛酮处理 6 0min后 ,下丘脑 (10 2 2± 1 2 2 )、纹状体(5 90± 0 84 )、脊髓 (2 99± 0 4 8)强啡肽原mRNA的相对含量低于吗啡依赖组 (均P <0 0 1) ,而垂体强啡肽原mRNA(2 6 72± 1 79)却高于吗啡依赖组 (11 6 0± 2 2 4 ,P <0 0 1)。结论　慢性给予吗啡可影响大鼠强啡肽原mRNA的表达 ,从而参与吗啡依赖形成和戒断反应。ObjectiveTo investigate the expression of pro-dynorphin mRNA in rats following morphine dependence and abstinence. MethodsThe rats were rendered dependent by subcutaneous injections of increasing doses of morphine from 10 to 40 mg/kg for 6 consecutive days. The rats as controls were administered similar volume of normal saline. The expression of pro-dynorphin mRNA was assayed using radioactive 32 P-labelled pro-dynorphin cDNA probe by Northern blot hybridization. Results Comparing with the expression level of pro-dynorphin in hypothalamus (34.36±1.46), striatum (31.24±2.83) and spinal cord (27.60±2.89) in control rats, the expression levels of pro-dynorphin in hypothalamus (23.88±1.62), striatum (19.87±2.03) and spinal cord (13.36±1.46) decreased significantly after chronic administration of morphine. However, the expression levels of pro-dynorphin in hippocampus increased from (25.87±1.74) to (29.67±3.23) after morphine treatment. After 60 minutes of naloxone administration, the expression levels of pro-dynorphin mRNA in hypothalamus (10.22±1.22), striatum (5.90±0.84) and spinal cord (2.99±0.48) were lower, while higher in pituitary (26.72±1.79) than that in morphine dependent rats. ConclusionChronic exposure to morphine appears to induce modification of endogeneous dynorphin system of rats, which contributes to the development of morphine dependence and precipitation of abstinence syndrome.

关 键 词：吗啡依赖 戒断 大鼠 强啡肽 MRNA 表达 影响 

分 类 号：R749.6[医药卫生—神经病学与精神病学]