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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”。
Objective To observe the effect of chronic intervention of CCK-8 and its receptor antagonist on withdrawal symptoms in morphine-dependent rats and observe the effect of CCK-8 on μ-opioid receptor binding in vitro To investigate the effects of CCK-8 on morphine dependence and its related receptor mechanisms. Methods To establish morphine-dependent rats and withdrawal of naloxone withdrawal model, CCK-8 and CCK1 receptor antagonist devazepide into the lateral ventricle and the chronic intervention of CCK2 receptor antagonist LY-288,513 to observe their effects on withdrawal symptoms. Radioligand binding assay in vitro detection of CCK-8 mu opioid receptor binding characteristics. Results ①In the first 10 minutes before morphine injection, CCK-8 and CCK receptor antagonist devazepide, LY-288,513 chronic intervention can reduce morphine withdrawal symptoms withdrawal symptoms, and can significantly reduce weight loss, jump, tremor (P <0.01). ②10-8 ~ 10-6 mol.L-1 CCK-8 can inhibit rat brain tissue dose-dependently μ opioid receptor binding to its ligand (P <0.01), and decreased the Bmax value of mu opioid receptor binding reaction, but had no effect on the Kd value. The inhibitory effect was reversed by CCK1 and CCK2 receptor antagonists (P < 0.01). Conclusion Chronic CCK-8 and its receptor antagonist can both reduce withdrawal symptoms in morphine-dependent rats. By inhibiting the binding of mu opioid receptor to its ligand, CCK-8 can reduce the Bmax value of mu opioid receptor, “Anti-opium effect.”