Wen D, Sun D, Zang G, Hao L, Liu X, Yu F, Ma C, Cong B
Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
Neuroscience. 2014 Sep 26;277:14-25. doi: 10.1016/j.neuroscience.2014.06.048. Epub 2014 Jun 30.
Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction.
胆囊收缩素八肽（CCK - 8）是一种脑肠肽，在多种阿片类成瘾行为中起重要作用。我们之前报道过CCK - 8可减弱吗啡诱导的条件性位置偏爱行为的表达及复现。CCK - 8对药物戒断负面情感成分的可能影响尚不清楚。目前尚无研究评估CCK - 8对吗啡戒断动物的情绪症状（如焦虑）的影响。我们使用高架十字迷宫研究了CCK - 8对吗啡戒断大鼠焦虑样行为的影响。吗啡戒断引发了时间依赖性的焦虑样行为，在第10天（吗啡依赖诱导后5天）达到峰值效应。CCK - 8（0.1和1μg，脑室内注射）治疗以剂量依赖性方式阻断了这种焦虑。CCK1受体拮抗剂（L - 364,718，10μg，脑室内注射）阻断了CCK - 8的作用。用CTAP（10μg，脑室内注射）进行μ阿片受体拮抗作用降低了“抗焦虑”作用。CCK - 8通过上调大鼠体内的内源性阿片类物质，经由CCK1受体抑制吗啡戒断大鼠的焦虑样行为。本研究明确确定了CCK - 8的独特功能以及中枢CCK1受体作为旨在改善药物成瘾的药物的潜在治疗靶点。
