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

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.