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褪黑素增加吗啡依赖小鼠下丘脑弓状核β - 内啡肽的表达

魏义明, 许盈, 俞昌喜, 韩静

福建医科大学 药学院药理学系； 基础医学院生理与病理生理学系，福州 350004

摘要

本文旨在考察褪黑素(melatonin, MEL)对吗啡依赖形成的作用。昆明小鼠皮下注射吗啡的同时腹腔注射MEL，连续 8 天，形成吗啡依赖，第8 天最后一次吗啡注射后2 h，皮下注射纳洛酮催促戒断。采用免疫组织化学和RT-PCR 法，结 合计算机图像处理技术，测定MEL 对吗啡依赖小鼠下丘脑弓状核(hypothalamic arcuate nucleus, ARH)中β- 内啡肽(β-endorphin, β-EP)表达的影响。结果显示，连续8 d 给予MEL (20 mg/kg)，在显著抑制吗啡依赖小鼠纳洛酮催促戒断症状的同时 (P<0.05)，可显著增强ARH 中β-EP 样免疫阳性反应强度及β-EP 前体物阿黑皮素原(proopiomelanocortin, POMC) mRNA的表 达(P<0.05)。上述结果提示，MEL 可促进ARH 中β-EP 的生成，这可能是其抑制小鼠吗啡依赖性形成的机制之一。

关键词： 褪黑素; 吗啡依赖; 下丘脑弓状核; β - 内啡肽; 阿黑皮素原

分类号：Q189

Melatonin enhances the expression of β-endorphin in hypothalamic arcuate nucleus of morphine-dependent mice

WEI Yi-Ming, XU Ying, YU Chang-Xi, HAN Jing

Department of Pharmacology； Department of Physiology and Pathophysiology, College of Preclinical Medicine, Fujian Medical University, Fuzhou 350004, China

Abstract

The study was conducted to investigate the effect of melatonin (MEL) on the expression of β-endorphin (β-EP) in the hypothalamic arcuate nucleus (ARH) of morphine-dependent mice. For a period of 8 consecutive days, male Kunming strain mice were injected subcutaneously (s.c.) with normal saline or increasing doses (10-80 mg/kg) of morphine, and intraperitoneally (i.p.) with MEL (10, 20 or 40 mg/kg) or vehicle (5% ethanol saline) simultaneously. Withdrawal response was induced by naloxone (3 mg/kg, s.c.) at 2 h after final morphine injection on the 8th day. The potency of withdrawal response was evaluated according to the jumping times and the body weight loss. After that, the expressions of β-EP and proopiomelanocortin (POMC) mRNA in ARH were examined by immunohistochemistry and RT-PCR, respectively. The results showed that MEL (i.p., 20 mg/kg) decreased the naloxone-precipitated withdrawal responses in morphine-dependent mice significantly (P<0.05). Meanwhile, MEL increased the intensity of β-EP-like immunoreactivity and enhanced the expression of POMC mRNA in ARH (P<0.05). These results suggest that MEL increases the expression of β-EP in ARH of morphine-dependent mice, which may partly contribute to the action of MEL to inhibit the development of morphine dependence.

Key words: Melatonin; morphine dependence; hypothalamic arcuate nucleus; β-endorphin; proopiomelanocortin

收稿日期：2008-08-22　　录用日期：2009-04-15

通讯作者：俞昌喜　　E-mail: changxiyu@mail.fjmu.edu.cn

引用本文：

魏义明, 许盈, 俞昌喜, 韩静. 褪黑素增加吗啡依赖小鼠下丘脑弓状核β - 内啡肽的表达[J]. 生理学报 2009; 61 (3): 255-262.

WEI Yi-Ming, XU Ying, YU Chang-Xi, HAN Jing. Melatonin enhances the expression of β-endorphin in hypothalamic arcuate nucleus of morphine-dependent mice. Acta Physiol Sin 2009; 61 (3): 255-262 (in Chinese with English abstract).