Sex differences in morphine dependence and plasma levels of morphine and morphine-3-glucuronide in rats

作     者：孙莉 贺瑞英 李潇潇 刘丽京 邓艳萍 

作者机构：北京大学中国药物依赖性研究所北京100191 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2014年第23卷第2期

页      面：124-131页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：National Science and Technology Support Program of China(Grant No.2008BAI49B01) the National Basic Research Program of China(Grant No.2009CB522000) 

主　　题：Sex differences Substance withdrawal syndrome Pharmacokinetics Morphine Morphine-3-glucuronide 

摘      要：To examine whether there are sex differences in morphine dependence and its metabolism. Naloxone-precipitated withdrawal study was performed. Twenty rats were induced by naloxone 1 h after a single dose of morphine injection. The withdrawal syndromes were recorded and an HPLC-UV method was set up to quantify the plasma levels of morphine and morphine-3-glucuronide（M3G）. In the spontaneous withdrawal study, 97 rats were treated with progressive morphine for 28 d to develop physical dependence. The spontaneous withdrawal syndromes were recorded and plasma levels of morphine and M3G were determined after the last injection. No significant differences were observed in withdrawal syndrome of naloxone precipitating. More severe spontaneous withdrawal syndromes were produced by chronic morphine injection in male rats than in female rats（P0.05）. Higher maximum plasma concentration（Cmax） of morphine was measured in male rats than female rats, while female rats had higher Cmax of M3G than male rats in both acute and chronic morphine administration. Our results indicated that sex differences existed in withdrawal syndrome of morphine-dependent rats, and the pharmacokinetics of morphine showed sex difference by both acute and chronic administration. There might be a relationship between the severity of withdrawal syndrome and the plasma concentrations of morphine, M3G, and the ratio of morphine to M3G（M3G/MOR）.