孤啡肽与八肽胆囊收缩素在大鼠脑内拮抗吗啡镇痛的协同作用

目的观察孤啡肽（ＯＦＱ）和八肽胆囊收缩素（ＣＣＫ ８）在大鼠脑内拮抗吗啡镇痛是否具有协同作用。方法应用等高线法设计实验，用辐射热甩尾法测定痛阈。皮下注射吗啡（５ｍｇ·ｋｇ－１）２０ｍｉｎ之后，选择有明显镇痛效应的大鼠，侧脑室（ｉｃｖ）分别注射不同剂量的ＯＦＱ和ＣＣＫ ８以及由两者不同比例（５∶１，２５∶１）不同剂量组成的混合物，观察对吗啡镇痛效应的影响。结果联合应用ＯＦＱ和ＣＣＫ ８所产生的抗吗啡镇痛作用明显大于单独使用ＯＦＱ或ＣＣＫ ８。结论ＯＦＱ和ＣＣＫ ８在一定比例、一定剂量组合范围内，对抗吗啡镇痛具有协同效应。

OFQ and CCK 8 act synergistically in antagonizing morphine analgesia in rats

AIM To study whether a synergistic interaction exists between opanin FQ (OFQ), the endogenous ligand of orphanin opioid receptor like receptor (ORL1), and cholecystokinin octapeptide (CCK 8) in antagonizing morphine induced analgesia (MIA). METHODS Experiments were designed by the isobole method, using radiant heat induced tail flick latency as indication of nociception. After subcutaneous (sc) injection of morphine (5 mg·kg -1 ), efficacious rats of morphine analgesia were injected intracerebroventricularly (icv) with normal saline, OFQ, CCK 8 and a mixture of OFQ and CCK 8 in various proportions and doses to observe the effect on antagonizing MIA. RESULTS It was revealed that icv Co administration OFQ and CCK 8 in a 5∶1 (ng) ratio or 2 5∶1 (ng) ratio produced a synergistic effect on reversing MIA. CONCLUSION OFQ and CCK 8 may produce synergistic interaction in antagonizing MIA, at least in certain dose ratio.