吗啡依赖及戒断对大鼠海马内神经甾体水平的影响  

The Effect of Morphine Dependence and Withdrawal on the Levels of Neurosteroids in Hippocampus of Male Rat

作　　者：王娜[1] 吴红海[1] 侯艳宁[1] 

机构地区：[1]白求恩国际和平医院药学部,石家庄050082

出　　处：《中国心理卫生杂志》2006年第7期430-433,共4页Chinese Mental Health Journal

基　　金：河北省自然科学基金资助项目(C2005000834)

摘　　要：目的：探讨吗啡躯体依赖、精神依赖及戒断对雄性大鼠海马内神经甾体水平的影响。方法：腹腔注射递增剂量吗啡建立大鼠吗啡躯体依赖模型，纳洛酮诱发戒断症状；条件性位置偏爱实验建立吗啡精神依赖模型。高效液相色谱-质谱法测定大鼠海马和血浆中脱氢表雄酮（DHEA）及其硫酸酯（DHEAS）、孕烯醇酮（PREG）及其硫酸酯（PREGS）和别孕烯醇酮（AP）含量。结果：大鼠吗啡躯体依赖形成时海马内DHEA、PREG水平较对照组升高（0．88±0．19／0．67±0．17，t=2．52，P〈0．05，10．94±2．02／7．53±2．64，t=3．24，P〈0．01），血浆中DHEAS、PREGS水平较对照组升高（115．4±99．7／29．3±8．3，t=3．20，P〈0．01；234．5±216．1／38．2±18．8，t=3．39，P〈0．01）；大鼠吗啡精神依赖形成时海马及血浆中DHEA水平降低（0．90±0．55，15．6±5．0／1．63±0．76，24．5±9．8，t=2．42，2．69，P〈0．05），血浆中DHEAS水平显著升高（187．4±44．8／136．7±30．7，t=2．88，P〈0．05）。与纳洛酮对照组比较，大鼠吗啡戒断时海马内DHEA、AP、DHEAS、PREGS水平升高（t=2．33—3．96，P〈0．05），血浆中PREG、AP、DHEAS和PREGS水平升高（t=3．72～4．82，P〈0．01）。结论：吗啡依赖、戒断可影响大鼠海马内某些神经甾体的水平，表明内源性神经甾体可能参与吗啡依赖的形成。Objective： To investigate the effect of morphine dependence and withdrawal on the levels of neurosteroids in hippocampus of male rat. Methods： Rats were given （ ip ） increasing doses of morphine to form morphine physical dependence, withdrawal syndromes were precipitated by naloxone. The conditioned place preference （CPP） was used to establish morphine psychological dependence. The concentrations of dehydroepiandrosterone （ DHEA）, dehydroepiandrosterone sulfate （ DHEAS）, pregnenolone （PREG）, pregnenolone sulfate （PREGS）, and allopregnanolone （ AP ） in rat hippocampus and plasma were quantified by liquid chromatography-mass spectrometry. Results： The rat model of morphine physical and psychological dependence were successfully established by ip increasing doses of morphine for 7 days and 5mg · kg^-1 morphine for 10 days respectively. Compared with saline control group, morphine physical dependence increased DHEA and PREG contents in rat hippocampus （0. 88 ±0. 19/0. 67 ±0. 17, t = 2. 52, 10.94± 2.02/7. 53 ± 2.64, t = 3.24, P 〈 0. 05, P 〈 0. 01 ）, increased DHEAS and PREGS concentrations in rat plasma （ 115.4 ±99. 7/29. 3 ±8. 3, t =3. 20, 234. 5 ±216. 1/38.2± 18. 8, t =3.39, P 〈0. 01 ） ; whereas morphine psychological dependence decreased DHEA content in rat hippocampus and plasma （0. 90 ±0. 55, 15.6 ±5.0/ 1.63 ± 0. 76, 24. 5 ± 9. 8, t = 2. 42, 2. 69, P 〈 0. 05 ）, but increased DHEAS concentration in rat plasma （ 187.4 ±44. 8/136. 7 ± 30. 7, t = 2.88, P 〈 0. 05 ） . Compared with naloxone-control group, morphine withdrawal increased the level of DHEA, AP, DHEAS, and PREGS in hippocampus It =2.33 -3.96, P 〈0.05, P 〈0.01 ）, also increased that of PREG, AP, DHEAS, and PREGS in rat plasma （ t = 3.72 - 4.82, P 〈 0. 01 ） . Conclusion： Chronic morphine and naloxone-induced morphine withdrawal could affect the contents of some neurosteroids in rat hippocampus, which suggests that endogenous neurosteroids in brain might be related to the

关 键 词：吗啡依赖 动物研究 戒断 神经甾体 海马 

分 类 号：R749.61[医药卫生—神经病学与精神病学]