吗啡依赖和复吸时大鼠脑内神经甾体水平的变化

目的探讨吗啡精神依赖和复吸对大鼠脑内神经甾体水平的影响。方法采用条件性位置偏爱(CPP)实验,吗啡诱导大鼠CPP形成,足底电击应激诱发CPP重建,高效液相色谱-质谱法测定大鼠额叶皮质、海马及血浆中孕烯醇酮(PREG)及其硫酸酯(PREGS)、别孕烯醇酮(AP)、脱氢表雄酮(DHEA)及其硫酸酯(DHEAS)的含量。结果5 mg.kg-1吗啡训练10 d诱导大鼠产生了稳定的CPP,间歇足底电击有效诱发CPP的重建。与对照组比较,吗啡CPP形成时,大鼠额叶皮质内DHEA、PREG水平升高(P<0.05),海马内DHEA水平降低(P<0.05);与吗啡消退组比较,足底电击诱发CPP重现时,大鼠额叶皮质内PREG水平降低(P<0.01),而海马内PREG水平升高(P<0.05)。结论大鼠额叶皮质和海马内神经甾体水平的变化可能与吗啡依赖和复吸有关。

Effect of morphine dependence and relapse on the levels of neurosteroids in male rat brain regions

Aim To investigate the effect of morphinedependence and relapse on the levels of neurosteroidsin male rat frontal cortex(Fc) and hippocampus(Hc).Methods Morphine-induced conditionedplace preference(CPP) paradigm in rat was used andfootshock stress was given to rats to reinstate morphineCPP.The contents of pregnenolone(PREG),preg-nenolone sulfate(PREGS),allopregnanolone(AP),dehydroepiandrosterone(DHEA),and dehydroepi-androsterone sulfate(DHEAS) in rat Fc homogenates,Hc homogenates and plasma were determined with liq-uid chromatography-mass spectrometry.Results 5 mg.kg-1morphine conditioning during 10 days resultedin acquisition of CPP and intermittent footshock reacti-vated morphine CPP following 7 days drug-free peri-ods.Compared with saline group,morphine-inducedCPP elevated DHEA and PREG contents in Fc(P<0.05),while decreased DHEA level in Hc(P<0.05);Compared with morphine extinct group,foot-shock-reinstated morphine CPP decreased PREG con-tent in Fc(P<0.01),but elevated PREG content inHc(P<0.05).Conclusion The changes of neuros-teroids in ratFc and Hc may be related to the formationand relapse of morphine dependence.