Clonidine attenuates naloxone-induced opioid-withdrawal syndrome in cholestatic mice
Clonidine attenuates naloxone-induced opioid-withdrawal syndrome in cholestatic mice
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DOI：
10.1034/j.1600-0773.2001.d01-146.x
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发表时间：
2001-09-01
期刊：
影响因子：
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通讯作者：
Namiranian, K
中科院分区：
文献类型：
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作者：
Dehpour, AR;Samini, M;Namiranian, K
胆汁淤积与血浆内源性阿片肽水平升高有关。纳洛酮沉淀性戒断综合征已在急性胆汁淤积症小鼠模型中被描述。因此，我们的目标是确定中枢去甲肾上腺素能过度活动是否参与阻塞性胆汁淤积症小鼠纳洛酮催促戒断综合征的表现。通过切除胆管建立小鼠急性胆汁淤积模型，并于诱导胆汁淤积后5d腹腔注射纳洛酮(2 mg/kg)诱发戒断症状，观察小鼠对身体的依赖。腹腔注射可乐定(0.1 mg/kg，α(2)-肾上腺素能受体激动剂)，15分钟。在注射纳洛酮之前，显著减轻胆汁淤积症小鼠的戒断严重程度。然而，用α(2)-肾上腺素受体拮抗剂育亨宾(3 mg/kg，腹腔注射)对动物进行15分钟的预处理。在可乐定阻断可乐定的这种改善作用之前。这项研究的结果支持了α(2)-肾上腺素能受体参与胆汁淤积症戒断综合征小鼠模型的证据。
Cholestasis is associated with elevated plasma level of endogenous opioid peptides. Naloxone-precipitated withdrawal syndrome has been described in a mouse model of acute cholestasis. Thus we aimed at determining whether central noradrenergic hyperactivity is involved in manifestation of naloxone-precipitated withdrawal syndrome in mice with obstructive cholestasis. Acute cholestasis was induced by bile duct resection in mice and physical dependence was observed by precipitating a withdrawal syndrome with naloxone (2 mg/kg, intraperitoneally) 5 days after induction of cholestasis. Administration of clonidine (0.1 mg/kg, intraperitoneally), an alpha (2)-adrenoceptor agonist, 15 min. before naloxone injection significantly alleviates withdrawal severity in cholestatic mice. However, pretreatment of animals with yohimbine (3 mg/ kg, intraperitoneally), an alpha (2)-adrenoceptor antagonist, 15 min. before clonidine blocked this ameliorative effect of clonidine. The results of this study support the evidence for involvement of the alpha (2)-adrenoceptors in the withdrawal syndrome of cholestasis in a mouse model.