目的建立吗啡条件性位置偏爱(CPP)模型,观察不同剂量的外源性CCK-8对足底电击诱导的吗啡CPP重燃的影响,并探讨其相关机制。方法建立足底电击诱导的吗啡CPP重燃模型,在CPP重燃前给予侧脑室注射CCK-8(0.1、1μg),以观察外源性CCK-8对足底电击诱导吗啡CPP重燃的影响。另外,CPP重燃前共同给予侧脑室注射CCK-8和CCK受体拮抗剂(CCK1受体拮抗剂L-364,718、CCK2受体拮抗剂L-365,260)、CCK-8和阿片受体拮抗剂(非选择性阿片受体拮抗剂纳洛酮、高选择性μ阿片受体拮抗剂CTAP),以探讨CCK-8抑制足底电击诱导吗啡CPP重燃的相关机制。结果 1足底电击成功重燃CPP的表达,并且0.1和1μg CCK-8有效抑制了CPP重燃过程。2 CCK1受体拮抗剂L-364,718和阿片受体拮抗剂纳洛酮、CTAP均可阻断CCK-8对足底电击诱导吗啡CPP重燃的抑制作用。结论 CCK-8可以通过CCK1受体抑制足底电击诱导的吗啡CPP重燃,并且这种作用与阿片受体相关。
Aim To explore the effects of exogenous CCK-8 on foot shock primed reinstatement of morphine-induced CPP and its mechanism. Methods The mod-el of morphine induced conditioned place preference was established. Doses of CCK-8 (0. 1,1 μg) were given intracerebroventricularly before CPP reinstate-ment, and the effects of exogenous CCK-8 on foot shock primed reinstatement of morphine-induced CPP were examined. Furthermore, CCK receptor antago-nists ( CCK1 receptor antagonist L-364 ,718 and CCK2 receptor antagonist L-365 , 260 ) and opioid receptor antagonists ( opioid receptor antagonist naloxone andμ-opioid receptor antagonists CTAP) were co-administra-ted with CCK-8 before CPP reinstatement to explore the mechanisms of CCK-8 inhibiting foot shock primed re- instatement of morphine-induced CPP. Results ①Foot shock successfully provoked the reinstatement of CPP, and CCK-8 (0. 1,1 μg) effectively inhibited the reinstatement of morphine-induced CPP. ②CCK1 re-ceptor antagonist L-364 , 718 , opioid receptor antago-nists naloxone and CTAP could block the inhibitory effects of CCK-8 on foot shock primed reinstatement of morphine-induced CPP. ③ CCK-8 itself had no effect on sensitivity threshold of rats to foot shock. Conclu-sion CCK-8 can inhibit foot shock primed reinstate-ment of morphine-induced CPP via CCK1 receptor. This function of CCK-8 is related to opioid receptor.