Sex differences in morphine dependence and plasma levels of morphine and morphine3glucuronide in rats

To examine whether there are sex differences in morphine dependence and its metabolism. Naloxoneprecipitated 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 HPLCUV method was set up to quantify the plasma levels of morphine and morphine3glucuronide(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(P<0.05). Higher maximum plasma concentration(C_(max))of morphine was measured in male rats than female rats, while female rats had higher C_(max)of M3G than male rats in both acute and chronic morphine administration. Our results indicated that sex differences existed in withdrawal syndrome of morphinedependent 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).National Science and Technology Support Program of China,the National Basic Research Program of China中国科学引文数据库(CSCD)2124-1312