CREB_1蛋白在大鼠急、慢性吗啡依赖和戒断中的表达变化

Immunohistochemical expression of CREB_1 proteins in brain in acute or chronic morphine addiction and withdrawal in rats

目的研究急、慢性吗啡依赖和戒断对大鼠脑组织cAMP反应元件结合蛋白(CREB1)的表达调节作用。方法雄性SD大鼠36只,随机分为急性对照组、急性吗啡依赖组、急性吗啡戒断组、慢性对照组、慢性吗啡依赖组、慢性吗啡戒断组,每组6只。采用免疫组化方法测定不同脑区和核团CREB1蛋白表达水平。结果急性吗啡依赖和戒断抑制蓝斑CREB1蛋白表达。慢性吗啡依赖和戒断增加皮质、海马、蓝斑等脑区核团CREB1蛋白的表达,但是在慢性吗啡依赖和戒断时,伏隔核CREB1蛋白表达下降。结论急、慢性吗啡依赖和戒断时CREB1在大鼠皮质、海马、下丘脑、蓝斑、伏隔核等脑区的表达存在差异,可能与介导阿片类药物依赖信号转道通路的反应性不同有关。

Objective To investigate the changes in CREB1 proteins in five brain regions of rats with morphine addiction and withdrawal with the technique of immunohistochemistry. Methods Thirty six adult male Sprague-Dawley rats were randomly divided into six groups （n=6 for each）, i.e. acute morphine dependent group, acute abstinence group, acute control group, chronic morphine dependent group, chronic abstinence group and chronic control group. Animals in dependent groups and abstinence groups were administered with morphine by intraperitoneal injection till morphine dependent models were established. The rats in abstinence groups withdrawal syndromes were induced with naloxone 5mg/kg for 30min. The rats in control groups were injected with saline. All rats were sacrificed by decapitation. The coronal sections of discrete brain regions （hypothalamus, nucleus accumbens, prefrontal cortex, locus coeruleus, hippocampus） were obtained. The relative concentrations of CREB1 protein were determined with immunohistochemistry. Results In acute morphine dependent and abstinence groups, CREB1 protein decreased significantly compared with the acute control group in locus coenlleus （P〈0. 01）. In chronic morphine dependent and abstinence groups, CREB1 protein increased significantly in locus coeruleus, hippocampus and cortex compared with that of the chronic control group （P〈0.01）. CREB1 protein decreased significantly in nucleus accumbens compared with that of the chronic control group （P〈0. 05）. Condusion The morphine-induced CREB1 protein changes may reflect differential G protein-cAMP-CREB signal transduction pathways in morphine dependent and abstinence rats.