The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP
The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP
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外源CCK-8对吗啡诱导的CPP获得和表达的影响
DOI：
10.1016/j.neulet.2011.12.063
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发表时间：
2012-02-21
影响因子：
2.5
通讯作者：
Li, Shujin
中科院分区：
文献类型：
--
作者：
Wen, Di;Cong, Bin;Li, Shujin
八肽胆囊收缩素（cholestokinin octapeptide，CCK-8）是最强的内源性抗阿片肽，调节多种生理过程。在我们以前的研究中，我们发现，外源性CCK-8减轻纳洛酮诱导的戒断症状，但CCK-8对吗啡的奖励效应的可能调节作用没有检查。本研究采用无偏条件位置偏爱（CPP）实验范式，探讨不同剂量的外源性CCK-8对吗啡奖赏效应的影响。因此，我们研究了CCK-8对吗啡诱导的CPP的获得、表达和消退以及对自发活动的影响。结果表明：CCK-8（0.01 ~ 1 μ g，i. c. v.）单独给药时，既不诱导CPP也不诱导位置厌恶，但当与10 mg/kg吗啡一起给药时，可阻断CPP的获得。在CPP测试前给予最高剂量的CCK-8（1 μ g）增加CPP，并且沿着较低剂量（0.1 μ g）减少其消退。此外，最高剂量（1 μ g）的CCK-8抑制自发活动。本研究首次提供了外源性CCK-8抑制奖赏活动的行为学证据，揭示了外源性CCK-8对位置偏爱的不同阶段和阿片依赖的发展具有显著影响。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Cholecystokinin octapeptide (CCK-8) is the most potent endogenous anti-opioid peptide and regulates a variety of physiological processes. In our previous study, we found that exogenous CCK-8 attenuated naloxone-induced withdrawal symptoms, but the possible regulative effects of CCK-8 on the rewarding effects of morphine were not examined. In the present study, we aimed to determine the exact effects of exogenous CCK-8 at various doses on the rewarding action of morphine by utilizing the unbiased conditioned place preference (CPP) paradigm. We therefore examined the effects of CCK-8 on the acquisition, expression and extinction of morphine-induced CPP and on locomotor activity. The results showed that CCK-8 (0.01-1 mu g, i.c.v.), administered alone, induced neither CPP nor place aversion, but blocked the acquisition of CPP when administered with 10 mg/kg morphine. The highest dose of CCK-8 (1 mu g) administered before CPP testing increased CPP and, along with lower doses (0.1 mu g), reduced its extinction. In addition, the highest dose (1 mu g) of CCK-8 suppressed locomotor activity. Our study provides the first behavioral evidence for the inhibitory effects of exogenous CCK-8 on rewarding activity and reveals significant effects of exogenous CCK-8 on various stages of place preference and the development of opioid dependence. (C) 2012 Elsevier Ireland Ltd. All rights reserved.