吗啡戒断性焦虑大鼠边缘系统CaMK Ⅱ含量及其磷酸化水平的改变

VARIABLE CONTENTS AND PHOSPHORYLASE LEVELS OF CaMK Ⅱ IN MORPHINE WITHDRAWAL RATS ASSOCIATED WITH LIMBIC SYSTEM

目的:观察吗啡戒断大鼠焦虑产生时其边缘系统主要脑区/核团、海马、杏仁核、前额叶皮质神经细胞CaMK Ⅱ的含量和磷酸化水平的改变。方法:48只大鼠随机分为生理盐水对照组(n=18)、模型组(n=18)、丁螺环酮组(n=12)。模型组和丁螺环酮组用剂量递增法建立大鼠吗啡依赖模型,停药后,丁螺环酮组给予丁螺环酮,模型组给予生理盐水。在吗啡自然戒断的72 h,用高架十字迷宫检测其焦虑行为,然后再用蛋白免疫印迹技术检测各组大鼠海马、杏仁核、前额叶皮质神经细胞CaMK Ⅱ的含量和磷酸化水平。结果:与生理盐水对照组和丁螺环酮组比较,模型组CaMK Ⅱ蛋白含量和β亚基磷酸化水平均显著升高(均P<0.01)。结论:吗啡戒断大鼠的边缘系统海马、杏仁核、前额叶皮质神经细胞CaMK Ⅱ含量、CaMK Ⅱβ亚基磷酸化水平的增高,这可能是吗啡依赖戒断焦虑行为产生的分子机制之一。

Objective： The variations of calmodlin - dependent protein kinase Ⅱ （ CaMK II） of the hippocampus, the amygdala and the prefrontal lobe cortex were detected in morphine withdrawal rats. Methods：Forty eight rats were randomly divided into three groups： the model （n = 18 ）, the control （n = 18 ） and the buspirone（ n = 12）. Gradually increasing dosage was used to establish morphine -dependent rats model, and then natural withdrawal was conducted, but he buspirone group was administered buspirone during morphine withdrawal. At 72 h of the withdrawal, all rats in different groups were validated for anxiety in the elevated plus maze. Western blot was used to detect the contents and the phosphorylase levels of CaMK Ⅱin the hippocampus, amygdale and prefrontal lobe cortex. Results： Compared with the control and the buspirone groups, higher content and phosphorylase level of β- subunit of CaMK Ⅱ were observed in the rats with morphine -withdrawal（ P 〈 0. 01 ）. Conclusion：Diverse content and phosphorylase level of β- subunit of CaMK Ⅱ in morphine dependent rats is found which may be contributed to anxious symptoms.