中文摘要：

目的：观察八肽胆囊收缩素（CCK-8）及其受体拮抗剂对吗啡戒断大鼠额叶皮质和海马cAMP反应元件结合蛋白（CREB）表达及其磷酸化（pCREB）的影响，初步探讨CCK-8调节吗啡戒断大鼠的受体后机制。方法：建立大鼠吗啡慢性依赖及纳络酮催促戒断模型，并给予CCK-8、CCK1受体拮抗剂L-364718和CCK2受体拮抗剂LY-288513慢性干预，应用Western blotting和免疫组织化学技术观察额叶皮质和海马CREB与pCREB 表达的变化。结果：（1）正常组大鼠额叶皮质神经元胞浆、胞核均表达CREB蛋白，pCREB蛋白则仅在胞核中高表达；海马CA1区锥体细胞层神经元中，CREB蛋白在胞浆中高表达，胞核低表达，pCREB蛋白则仅在胞核中表达。（2）慢性吗啡作用后CREB无明显变化， pCREB增加；急性纳洛酮催促戒断后CREB仍无明显变化， pCREB进一步升高。（3）与戒断组相比，CCK-8、L-364718和LY-288513慢性干预对吗啡依赖戒断大鼠额叶皮质CREB蛋白表达无明显影响，pCREB蛋白表达均明显降低；L-364718和LY-288513慢性干预后，海马CREB与pCREB表达均明显降低，而CCK-8慢性干预对CREB蛋白表达无明显影响，仅pCREB蛋白表达明显降低。结论：CCK-8及其受体拮抗剂可能通过调节核转录因子CREB减轻吗啡戒断症状，并具有脑区特异性。

英文摘要：

AIM：To observe the effects of cholecystokinin octapeptide （CCK-8） and its receptor antagonists on cAMP response element binding protein （ CREB） and phosphorylated CREB （ pCREB） expression in frontal cortex and hippocampus of morphine withdrawal rats , which aim to explore the post-receptor mechanism through which CCK-8 regu-lates morphine withdrawal .METHODS： After the morphine dependence and naloxone-precipitated withdrawal animal models were established, the effects of CCK-8, L-364718 （CCK1 receptor antagonist） and LY-288513 （CCK2 receptor an-tagonist） pretreatment on CREB and pCREB expression in frontal cortex and hippocampus were observed by Western blot -ting and immunohistochemistry .RESULTS：In rat frontal cortex neuron , CREB was expressed in both cytoplasm and nu-cleus, but pCREB was only highly expressed in the nucleus .In the pyramidal cell layer of hippocampal CA 1 region, CREB showed high expression in the cytoplasm and low expression in the nucleus , while pCREB was only expressed in the nu-cleus.No obvious change of CREB was observed after either chronic morphine treatment or naloxone withdrawal .The pCREB expression was increased after chronic morphine treatment and further increased after naloxone withdrawal .Com-pared with the withdrawal group , chronic pretreatment with CCK-8, L-364718 and LY-288513 had no effect on CREB expression in the frontal cortex , but obviously decreased the pCREB expression .In the hippocampus , pretreatment with L-364718 and LY-288513 decreased CREB and pCREB expression , but only the pCREB expression was decreased after CCK-8 treatment.CONCLUSION：CCK-8 and CCK receptor antagonists may alleviate morphine withdrawal symptoms by regulating CREB , with specificity in different brain regions .