酒精依赖大鼠皮质CREB变化及氟西汀对其影响

目的　研究酒依赖大鼠皮质cAMP反应元件结合蛋白 (CREB)、磷酸化CREB( p CREB)蛋白表达的变化 ,并观察氟西汀对其影响。方法　给大鼠自由饮含低浓度乙醇 (体积分数为 6% )的水溶液 2 8d。采用免疫组织化学方法检测大鼠皮质CREB、p CREB蛋白表达。结果　撤除酒精后大鼠前额皮质、梨状皮质的p CREB蛋白表达均降低 ,其中以戒断 2 4h时降低最明显 ,与对照组比较两部位分别降低5 7 2 8%、5 5 84%。氟西汀 ( 10mg·kg-1,ip)能减轻饮酒大鼠戒断症状 ,增加大鼠戒断 2 4h时前额皮质、梨状皮质 p CREB水平 ,与饮酒组戒断 2 4h比较两部位分别增加2 92 5 8%、12 8 44 %。结论　CREB可能是介导酒精依赖的受体后信号转导物质之一 ,氟西汀对酒精戒断症状的改善与其拮抗酒精戒断诱导的 p CREB降低有关

Changes of CREB in brain cortex of ethanol dependent rats and effect of fluoxetine

AIM To investgate the changes in the expression of CREB and p-CREB in the cortex of ethanol dependent rats. On other hand, the effects of fluoxetine on these changes were also studied. METHODS Ethanol was administered in drinking water at the concentration of 6% V/V, for 28 d. The expression of CREB and p-CREB in the rat cortex were measured by immunohistochemistry methods. RESULTS It was found that chronic ethanol treatment and its withdrawal did not modify the expression of CREB in the rat cortex. However, the levels of p-CREB in the frontal and piriform cortex of rats were significantly decreased during ethanol withdrawal, and respectively decreased 57.28%?55.84% compared to control rats at 24 h after ethanol withdrawal. When fluoxetine (ip, 10 mg·kg -1) were administried concurrently with ethanol, it can significantly dampen alcohol withdrawal symptoms and antagonize the down-regulation of the phosphorylation of CREB in the frontal and piriform cortex of rats at 24 h after ethanol withdrawal, the expression of p-CREB protein respectively increased 292 58%,128 44% compared with rats intaking ethanol. CONCLUSION CREB may be one of the substance of the signal transduction process for ethanol dependence. Fluoxetine can reverse the decreased p-CREB levels in rat cortex induced by ethanol withdrawal, which may be the part reason of fluoxetine dampening alcohol withdrawal symptoms.