吗啡依赖大鼠额叶皮质内神经甾体水平的变化

Changes on the Levels of Neurosteroids in Morphine Dependent Rat Frontal Cortex

目的探讨吗啡依赖和戒断对雄性大鼠额叶皮质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-质谱法测定大鼠额叶皮质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)的含量。结果与对照组比较,大鼠吗啡躯体依赖形成时额叶皮质内DHEA水平显著升高(P<0.05),精神依赖形成时额叶皮质内DHEA,PREG水平显著升高(P<0.05);与纳洛酮对照组比较,纳洛酮催促吗啡戒断时大鼠额叶皮质内PREG,AP的含量显著升高(P<0.01),DHEAS水平显著降低(P<0.05)。结论吗啡依赖、戒断可影响大鼠额叶皮质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 male rat frontal cortex.METHODS Increasing doses of morphine were given （ip） to rats to induce morphine physical dependence model and the withdrawal syndromes were precipitated by naloxone. Conditioned place preference（CPP） was used to establish the morphine psychical dependence. The concentrations of pregnenolone （PREG）, dehydroepiandrosterone （DHEA）, allopregnanolone （AP）, dehydroepiandrosterone sulfate （DHEAS） and pregnenolone sulfate（PREGS） in frontal cortex and plasma of rats were quantified by liquid chromatography mass spectrometry. RESULTS Compared with saline control group, morphine physical dependence increased the content of DHEA in rat frontal cortex （ P 〈 0.05） ; morphine-induced CPP increased the concentrations of DHEA and PREG in rat frontal cortex（ P 〈 0.05）. Compared with naloxone-control group, naloxone-induced morphine withdrawal increased the levels of PREG and AP（ P 〈 0.01 ）, decreased that of DHEAS in frontal cortex（ P 〈 0.05）. CONCLUSION Morphine dependence and naloxone-induced withdrawal affect the levels of some neurosteroids in rat frontal cortex, which suggest that endogenous neurosteroids in brain might be related to the development of morphine dependence and withdrawal.