环磷酸腺苷反应元件结合蛋白在吗啡依赖及戒断大鼠脑区的表达

Expression of cAMP response element binding protein in some brain regions of morphine-dependence rats

目的 研究吗啡依赖及吗啡戒断时环磷酸腺苷反应元件结合蛋白 (CREB)在大鼠脑内的表达。方法 将 1 5只雄性Sprague Dawley大鼠随机分为正常对照组、吗啡依赖组和吗啡戒断组 ,每组各 5只。于大鼠背部皮下注射吗啡 ,第 1天注射 2 0mg/kg ,逐日递增剂量 ,至第 5天达 1 0 0mg/kg ,形成大鼠吗啡依赖模型。吗啡戒断组大鼠在末次注射吗啡后 1 6h皮下注射纳洛酮 1mg/kg。采用免疫印迹法观察各组大鼠的前额叶皮质、伏隔核和海马等脑区CREB的表达。结果 (1 )在前额叶皮质 ,吗啡依赖组和吗啡戒断组CREB的含量 (为相对光密度值 )分别为 [(1 31± 1 1 ) % ]和 [(1 33± 1 5) % ] ,均高于正常对照组 [(1 0 0± 1 4 ) % ] ,差异有显著性 (P <0 0 5) ;(2 )在伏隔核 ,三组CREB的差异无显著性(P >0 0 5) ;(3)在海马 ,吗啡戒断组CREB的含量 [(1 4 1± 1 8) % ]高于正常对照组 [(1 0 0± 1 4 ) % ] ,差异有非常显著性 (P <0 0 1 )。结论 大鼠处于吗啡依赖和戒断时CREB的表达在前额叶皮质和海马发生改变 。

Objective To study the expression of cAMP response element binding protein (CREB) in some brain regions of morphine dependent and morphine withdrawal rats Methods Fifteen male Sprague Dawley rats were randomly divided into normal control group, morphine dependence group and morphine withdrawal group, 5 in each group To set up animal model of morphine dependence, the rats were subcutaneously injected with morphine 20 mg/kg on the first day, and gradually increased to 100 mg/kg on the fifth day Withdrawal symptoms were precipitated by subcutaneous injection of naloxone 1 mg/kg, 16 hours after the last dose of morphine The expression of CREB was investigated with Western blotting in prefrontal cortex, nucleus accumbens, and hippocampus Results The relative amount of CREB in prefrontal cortex was significantly higher in morphine dependence and morphine withdrawal rats [(131±11)% and (133±15)%, respectively] than in normal rats [(100±14)%; P <0 05] The CREB level in hippocampus was significantly higher in morphine withdrawal rats than in normal rats [(141±18)% vs (100±14)%, P <0 01] There was no significant difference in nucleus accumbens among the three groups ( P >0 05) Conclusion The levels of CREB are altered in prefrontal cortex and hippocampus of morphine dependence or morphine withdrawal rats, suggesting that the regulating of CREB expression in some brain regions may be involved in the development of opioid dependence