吗啡依赖对大鼠不同脑区内神经甾体水平的影响

目的建立大鼠条件性位置偏爱(CPP)模型，探讨吗啡精神依赖对大鼠脑内神经甾体水平的影响。方法 大鼠连续10 d腹腔注射吗啡5 mg·kg^-1，诱导CPP形成。高效液相色谱-质谱法测定大鼠伏隔核、杏仁核、下丘脑和血浆中脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯及孕烯醇酮硫酸酯的含量。结果经10 d吗啡训练后，吗啡组大鼠在伴药侧的停留时间显著长于对照组，吗啡诱导的大鼠CPP形成。与对照组相比，吗啡组大鼠下丘脑内孕烯醇酮明显降低，伏隔核和血浆中的脱氢表雄酮明显降低。结论吗啡诱导CPP形成，吗啡处理影响大鼠脑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。

Effects of morphine dependence on the levels of neurosteroids in rat brain

AIM: To establish the rat model of morphine-induced conditioned place preference (CPP) and to investigate the effects of morphine psychical dependence on the levels of neurosteroids in rat brain. METHODS: Rats were ip administered morphine 5 mg x kg(-1) for 10 days to induce CPP in morphine group. The concentrations of dehydroepiandrosterone (DHEA), pregnenolone (PREG), allopregnanolone (AP), dehydroepiandrosterone sulfate (DS) and pregnenolone sulfate (PS) in nucleus accumbens (Nac), hypothalamus (Ht), amygdale (A) and plasma of rats were determined with liquid chromatography-negative atmospheric pressure ionization mass spectrometry (LC-MS). RESULTS: Trained with morphine for 10 days resulted in the acquisition of CPP in morphine group with the time that the rats spent in drug-pairing room was longer than that of control group. Compared with control group, morphine treatment could significantly decrease the contents of DHEA in Nac and plasma, decrease that of PREG in Ht. CONCLUSION: Morphine could induce the CPP in rats and affected the contents of some neurosteroids in rat brain, which suggests that endogenous neurosteroids might he related to the development of morphine dependence.