生理学报Acta Physiologica Sinica, April

研究论文

急、 慢性乙醇处理后大鼠伏核内cAMP反应元件结合蛋白磷酸化的变化

李菁1，*, 李跃华1, 张小虎2, 朱学江2, 戈应滨2, 袁孝如2

南京医科大学 1病理学与病理生理学系, 2生理学系, 南京 210029

摘要: 采用免疫组织化学的方法, 检测急性、 慢性乙醇作用及戒断后大鼠伏核内cAMP反应元件结合蛋白(cAMP response element binding protein, CREB)磷酸化的变化。结果显示, 急性腹腔注射乙醇后15 min, 伏核内磷酸化CREB(phospho-CREB, p-CREB)蛋白明显增加, 30 min后达高峰, 至1和6 h后仍明显高于对照组。而慢性饮乙醇溶液显著降低大鼠伏核内p-CREB蛋白含量, 在撤除乙醇后24、 72 h时, 伏核内p-CREB蛋白含量仍明显较低, 戒断后7 d, 恢复到正常水平。结果表明, 急性乙醇处理增加伏核内CREB磷酸化作用, 而慢性乙醇作用则降低伏核内CREB磷酸化作用, 这可能是乙醇依赖的分子机制之一。

关键词: 乙醇; 伏核; cAMP反应元件结合蛋白

中图分类号: Q426; R338.2

Changes in the phosphorylation of cAMP response element binding protein in the rat nucleus accumbens after acute and chronic ethanol administration

LI Jing1,*, LI Yue-Hua1, ZHANG Xiao-Hu2, ZHU Xue-Jiang2, GE Ying-Bin2 , YUAN Xiao-Ru2

１Department of Pathology and Pathophysiology, and 2Department of Physiology, Nanjing Medical University, Nanjing 210029

Abstract: To define the molecular basis of ethanol dependence, changes in the phosphorylation of cAMP response element binding protein (CREB) in the nucleus accumbens of rats after acute and chronic ethanol administration were detected using immunohistochemistry. The results demonstrate that the expression of phospho-CREB (p-CREB) protein in the rat nucleus accumbens significantly increased after 15 min of acute ethanol exposure, reaching a peak at 30 min after ethanol administration. The increment remained after 1 or 6 h of ethanol exposure compared to the control rats. In contrast, chronic intake of ethanol solution obviously decreased the expression of p-CREB protein compared to the control rats. The decrement remained 24 h or 72 h after ethanol withdrawal, and returned to the control levels after 7 d of ethanol withdrawal. The results suggest that an acute ethanol administration led to an increase in the phosphorylation of CREB in the nucleus accumbens, but chronic ethanol administration produced a decrement, which is possibly one of the molecular mechanisms of alcohol dependence.

Key words: ethanol; nucleus accumbens; cAMP response element binding protein (CREB)