中文摘要：

目的观察侧脑室给予八肽胆囊收缩素（CCK-8）及其受体拮抗剂慢性干预对吗啡依赖大鼠戒断症状的影响,并在体外观察CCK-8对μ阿片受体结合反应的影响,初步探讨CCK-8对吗啡依赖过程的影响及其相关受体机制。方法建立大鼠吗啡依赖及纳络酮催促戒断模型,侧脑室注射CCK-8及CCK1受体拮抗剂devazepide、CCK2受体拮抗剂LY-288,513慢性干预,观察其对戒断症状的影响;应用放射配基结合实验体外检测CCK-8对μ阿片受体结合特征的影响。结果①吗啡注射前10 min侧脑室注射CCK-8和CCK受体拮抗剂devazepide、LY-288,513慢性干预均能降低吗啡依赖大鼠的戒断症状评分,并可明显改善体重下降、跳跃、齿颤、流涎等戒断症状,与戒断组相比差异均有显著性（P〈0.01）;②10-8～10-6 mol.L-1 CCK-8可以剂量依赖性地抑制大鼠脑组织中μ阿片受体与其配基的结合（P〈0.01）,降低μ阿片受体结合反应的Bmax值,而对Kd值无影响;且此抑制作用可被CCK1及CCK2受体拮抗剂翻转（P〈0.01）。结论 CCK-8及其受体拮抗剂慢性干预均能减轻吗啡依赖大鼠戒断症状;CCK-8通过抑制μ阿片受体与其配基的结合,降低μ阿片受体的Bmax值,发挥其＂抗阿片作用＂。

英文摘要：

Aim To explore the mechanisms of CCK-8 in morphine dependence development,the effect of CCK-8 and CCK receptor antagonists on morphine withdrawal rats was observed.Meanwhile,the effect of CCK-8 on binding affinity of μ-opioid receptor was detected.Methods After rats models were established for morphine dependence and naloxone-precipitated withdrawal,the effects of CCK-8,devazepide,a CCK1 receptor antagonist and LY-288,513,a CCK2 receptor antagonist given intracerebroventricularly on the morphine withdrawal symptom were observed,and the effects of CCK-8 on binding affinity of μ-opioid receptor were tested with radioligand binding assay.Results ① Intracerebroventricular injections of CCK-8 and CCK receptor antagonists 10 min before morphine treatments were able to drop the overall morphine withdrawal scores,and attenuated the symptoms of weight loss,jumping,teeth chattering and ptosis.② 10-8~10-6 mol·L-1 CCK-8 suppressed dose-dependently the binding of MOR,and significantly decreased the binding capacity（Bmax）,but not the binding affinity（Kd）.Furthermore,this effect could be reversed by CCK1 and CCK2 receptor antagonists.Conclusion Both CCK-8 and CCK receptor antagonists can alleviate withdrawal symptoms of morphine dependent rats,and CCK-8 exerts its anti-opioid effects by suppressing the binding of μ-opioid receptor and by decreasing the Bmax of μ-opioid receptor.