Pharmacokinetic aspects of naloxone-precipitated morphine withdrawal in male and female prepubertal mice
Pharmacokinetic aspects of naloxone-precipitated morphine withdrawal in male and female prepubertal mice
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DOI：
10.1002/bdd.554
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发表时间：
2007-09-01
影响因子：
2.1
通讯作者：
Balerio, Graciela N.
中科院分区：
文献类型：
--
作者：
Diaz, Silvina L.;Hermida, Maria P.;Balerio, Graciela N.
研究表明，由纳洛酮（NAL）引发的吗啡（MOR）戒断综合征在雄性小鼠中的表现比雌性小鼠更强烈，但这种现象的原因仍不清楚。本研究的目的是评估这种性别二态性是否可能是由于 MOR 长期治疗后 MOR 和/或 NAL 血浆水平的差异所致。青春期前的瑞士雄性和雌性小鼠通过腹膜内 (i.p.) 注射 MOR (2 mg/kg) 产生依赖性，每天两次，持续 9 天。第 10 天，依赖性小鼠在 MOR 注射后 60 分钟接受 NAL（6 mg/kg，腹腔注射）。在不同时间采集血样，以便分别通过气相色谱-质谱法（GC-MS）和高效液相色谱法（HPLC）测定MOR和NAL血浆水平。药代动力学分析显示雄性和雌性小鼠之间的 MOR 或 NAL 没有差异。总之，尽管男性和女性对 NAL 诱发的戒断反应不同，但这种二态性行为不会受到药代动力学因素的影响。版权所有 (c) 2007 John Wiley & Sons, Ltd.
It has been shown that the expression of the morphine (MOR) withdrawal syndrome precipitated by naloxone (NAL) is more intense in male mice than in females, but the reasons for this phenomenon remain uncertain. The purpose of the present study was to evaluate whether this sexual dimorphism might be due to differences in MOR and/or NAL plasma levels after a chronic treatment with MOR. Prepubertal Swiss male and female mice were rendered dependent by intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 days. On day 10 dependent mice received NAL (6 mg/kg, i.p.) 60 min after MOR injection. Blood samples were taken at different times in order to determine MOR and NAL plasma levels by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC), respectively. Pharmacokinetic analysis showed no differences between male and female mice either for MOR or for NAL. In conclusion, although males and females respond differentially to NAL-precipitated withdrawal, this dimorphic behavior would not be influenced by a pharmacokinetic factor. Copyright (c) 2007 John Wiley & Sons, Ltd.