吗啡处理大鼠的戒断症状以及血浆吗啡及其代谢物M3G含量的性别差异

doi:10.5246/jcps.2014.02.016

中国药学(英文版)

吗啡处理大鼠的戒断症状以及血浆吗啡及其代谢物M3G含量的性别差异

孙莉, 贺瑞英, 李潇潇, 刘丽京, 邓艳萍^*

北京大学中国药物依赖性研究所, 北京 100191

收稿日期:2013-05-13 修回日期:2013-06-02 出版日期:2014-02-15 发布日期:2014-01-25
通讯作者: 邓艳萍*
作者简介:*Corresponding author. Tel.: 86-10-82801340; E-mail: deng311@bjmu.edu.cn
基金资助:
National Science and Technology Support Program of China (Grant No. 2008BAI49B01) and the National Basic Research Program of China (Grant No. 2009CB522000).

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

Li Sun, Ruiying He, Xiaoxiao Li, Lijing Liu, Yanping Deng^*

National Institute on Drug Dependence, Peking University, Beijing 100191, China

Received:2013-05-13 Revised:2013-06-02 Online:2014-02-15 Published:2014-01-25
Contact: Yanping Deng*
About author:*Corresponding author. Tel.: 86-10-82801340; E-mail: deng311@bjmu.edu.cn
Supported by:
National Science and Technology Support Program of China (Grant No. 2008BAI49B01) and the National Basic Research Program of China (Grant No. 2009CB522000).

摘要/Abstract

摘要：

本文旨在评价阿片依赖行为是否存在性别差异。纳洛酮催促戒断研究: 20只大鼠, 单次注射吗啡后1小时注射纳洛酮。评价大鼠戒断症状, 同时应用HPLC-UV方法测定血浆中吗啡和M3G浓度。自然戒断研究: 97只大鼠, 吗啡组以剂量递增法给药28天, 于最后一次给药后, 评价大鼠自然戒断症状和血浆中吗啡以及M3G的含量。急性给药催促戒断的戒断症状未观察到性别差异。自然戒断后身体戒断症状存在性别差异, 雄鼠重于雌鼠 (P<0.05)。在急性给药实验和慢性给药实验中, 吗啡的C_max雄鼠比雌鼠含量高, M3G的C_max雌鼠比雄鼠含量高。吗啡药代动力学特征在急性给药实验和慢性给药实验中存在性别差异。成瘾大鼠自然戒断后身体戒断症状的程度和血浆中吗啡、M3G浓度以及M3G/MOR的比值相关。

关键词: 性别差异, 戒断症状, 药代动力学, 吗啡, 3-葡萄糖醛酸吗啡

Abstract:

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 (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 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).

Key words: Sex differences, Substance withdrawal syndrome, Pharmacokinetics, Morphine, Morphine-3-glucuronide

中图分类号:

R969.1

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

孙莉, 贺瑞英, 李潇潇, 刘丽京, 邓艳萍. 吗啡处理大鼠的戒断症状以及血浆吗啡及其代谢物M3G含量的性别差异[J]. 中国药学(英文版), DOI: 10.5246/jcps.2014.02.016.

Li Sun, Ruiying He, Xiaoxiao Li, Lijing Liu, Yanping Den . Sex differences in morphine dependence and plasma levels of morphine and morphine-3-glucuronide in rats[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.02.016.

参考文献

[1] Boyer, J.S.; Morgan, M.M.; Craft, R.M. Brain Res. 1998, 796, 315–318.

[2] Cook, C.D.; Barrett, A.C.; Roach, E.L.; Gowman, J.R.; Picker, M.J. Psychopharmacology. 2000, 150, 430–442.

[3] Krzanowska, E.K.; Bodnar, R.J. Brain Res. 1999, 821, 224–230.

[4] Craft, R.M.; Kalivas, P.W.; Stratmann, J.A. Behav. Pharmacol. 1996, 7, 764–778.

[5] Craft, R.M.; Heideman, L.M.; Bartok, R.E. Drug Alcohol. Depend. 1999, 53, 95–109.

[6] Cicero, T.J.; Nock, B.; Meyer, E.R. Pharmacol. Biochem. Behav. 2002, 72, 691–697.

[7] Craft, R.M.; Stratmann, J.A.; Bartok, R.E.; Walpole, T.I.; King, S.J. Psychopharmacology. 1999, 143, 1–7.

[8] Alexander, B.K.; Coambs, R.B.; Hadaway, P.F. Psychopharmacology. 1978, 58, 175–179.

[9] Cicero, T.J.; Ennis, T.; Ogden, J.; Meyer, E.R. Pharmacol. Biochem. Behav. 2000, 65, 91–96.

[10] Ali, B.H.; Sharif, S.I.; Elkadi, A. Clin. Exp. Pharmacol. Physiol. 1995, 22, 342–344.

[11] Craft, R.M.; Stratmann, J.A.; Bartok, R.E.; Walpole, T.I.; King, S.J. Psychopharmacology. 1999, 143, 1–7.

[12] Diaz, S.L.; Hermida, M.P.; Joannas, L.D.; Olivera, M.; Ridolfi, A.; Villaamil, E.C.; Balerio, G.N. Biopharm. Drug Dispos. 2007, 28, 283–289.

[13] Cicero, T.J.; Nock, B.; Meyer, E.R. J. Pharmacol. Exp. Ther. 1996, 279, 767–773.

[14] Cicero, T.J.; Nock, B.; Meyer, E.R. J. Pharmacol. Exp. Ther. 1997, 282, 939–944.

[15] McQuay, H.J.; Carroll, D.; Faura, C.C.; Gavaghan, D.J.; Hand, C.W.; Moore, R.A. Clin. Pharmacol. Ther. 1990, 48, 236–244.

[16] South, S.M.; Wright, A.W.; Lau, M.; Mather, L.E.; Smith, M.T. J. Pharmacol. Exp. Ther. 2001, 297, 446–457.

[17]Gellert, V.F.; Holtzman, S.G. J. Pharmacol. Exp. Ther. 1978, 205, 536–546.

[18] Cicero, T.J.; Meyer, E.R. J. Pharmacol. Exp. Ther. 1973, 184, 404–408.

[19] Cobuzzi, J.L.; Riley, A.L. Pharmacol. Biochem. Behav. 2011, 98, 28–34.

[20] Baker, L.; Ratka, A. Pain. 2002, 95, 65–74.

[21] Smith, M.T.; Walt, J.A.; Cramond, T. Life Sci. 1990, 47, 579–586.

[22] Gardmark, M.; Karlsson, M.O.; Jonsson, F.; Hammmarlund-Udenaes, M. J. Pharm. Sci. 1998, 7, 813–820.

[23] Kuo, C.K.; Hanioka, N.; Hashikawa, Y.; Oguri, K.; Yoshimura, H. J. Pharmacobiodyn. 1991, 14, 187–193.

[24] Gong, Q.; Hedner, J.; Bjorkman, R.; Hedner, T. Pain. 1992, 48, 249–255.

[25] Carter, A.; Soliman, M.R. Life Sci. 1998, 62, 93–101.

[26] Zubieta, J.K.; Smith, Y.R.; Bueller, J.A.; Xu, Y.; Kilbourn, M.R.; Jewett, D.M.; Meyer, C.R.; Koeppe, R.A.; Stohler, C.S. J. Neurosci. 2002, 22, 5100–5107.

[27] Cahill, L. Nat. Rev. Neurosci. 2006, 7, 477–484.

[28] Smith, Y.R.; Stohler, C.S.; Nichols, T.E.; Bueller, J.A.; Koeppe, R.A.; Zubieta, J.K. J. Neurosci. 2006, 26, 5777–5785.

[29] Hammer, R.P.; Zhou, L.; Cheung, S. Horm. Behav. 1994, 28, 431–43.

[30] Ratka, A.; Simpkins, J.W. Horm. Behav. 1991, 25, 217–228.

[31] Dahan, A.; Kest, B.; Waxman, A.R.; Sarton, E. Anesth. Analg 2008, 107, 83–95..

[32] Breedlove, S.M. Annu. Rev. Psychol. 1994, 45, 389–418.

[33] Rush, G.F.; Newton, J.F.; Hook, J.B. J. Pharmacol. Exp. Ther. 1983, 227, 658–662.

[34] Coffman, B.L.; Rios, G.R.; Tephly, T.R. Drug Metab. Dispos. 1996, 24, 329–333.

[35] King, C.D.; Rios, G.R.; Green, M.D.; MacKenzie, P.I.; Tephly, T.R. Drug Metab. Dispos. 1997, 25, 251–255.

[36] Huang, H.J.; Tsai, M.L.; Chen, Y.W.; Chen, S.H. J. Proteomics. 2011, 74, 2734–2744.

[37] Walker, E.A.; Sterious, S.N. Br. J. Pharmacol. 2005, 145, 975–983.

[38] Papaleo, F.; Ghozland, S.; Ingallinesi, M.; Roberts, A.J.; Koob, G.F.; Contarino, A. Neuropsychopharmacology. 2008, 33, 2878–2887.

[39] Kawasaki, Y.; Ishida, S.; Jin, C.; Kitamura, Y.; Kawasaki, H.; Gomita, Y.; Sendo, T.; Araki, H. Eur. J. Pharmacol. 2011, 666, 131–134.

吗啡处理大鼠的戒断症状以及血浆吗啡及其代谢物M3G含量的性别差异

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

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