酒精依赖和戒断时大鼠伏隔核、杏仁核区内神经甾体水平的变化

目的:采用♂大鼠酒精依赖模型,观察酒精依赖及戒断对大鼠伏隔核、杏仁核中不同神经甾体水平的影响。方法:通过大鼠自由饮含6%的乙醇溶液,连续42d使大鼠形成酒精依赖,并撤除酒精使其自然戒断。断头取脑分离取出伏隔核、杏仁核脑区。使用液液萃取和固相萃取两步法提取脑组织中的孕烯醇酮(PREG)、脱氢表雄酮(DHEA)、别孕烯醇酮(AP)、脱氢表雄酮硫酸酯(DHEAS)、孕烯醇酮硫酸酯(PREGS),以高效液相色谱-质谱联用法测定神经甾体含量。结果:与对照组相比,酒精依赖大鼠伏隔核DHEA,PREG,AP,DHEAS,PREGS的水平显著降低(P<0.05),杏仁核AP,PREGS的水平显著降低(P<0.05);酒精戒断6h大鼠伏隔核DHEA,DHEAS,PREGS的水平显著降低(P<0.05),杏仁核PREGS的水平显著降低(P<0.05);酒精戒断24h大鼠杏仁核DHEA的水平显著上升(P<0.05),伏隔核、杏仁核DHEAS、PREGS的水平显著下降(P<0.01)。结论:酒精依赖形成和戒断对伏隔核、杏仁核中的神经甾体水平有不同的影响,具有区域特异性。

EFFECT OF ETHANOL DEPENDENCE ON THE LEVELS OF NEUROSTEROIDS IN RAT NUCLEUS ACCMBENS AND AMYGDALA

Objective:To detect the effect of ethanol dependence and withdrawal on the levels of neurosteroids in nucleus accmbens,amygdala in rat ethanol dependent model. Methods: The brain samples were dissected out from ethanol dependent and withdrawal rats treated with liquid containing 6% ethanol for 42 days. Neurosteroids were isolated in a two-step procedure. The contents of neurosteroids including pregnenolone(PREG),dehydroepiandrosterone (DHEA),allopregnanolone(AP),pregnenolone sulfate(PREGS), dehydroepiandrosterone sulfate(DHEAS) were determined with liquid chromatography-negative atmospheric pressure chemical ionization mass spectrometry(LC-MS). Results: Chronic ethanol administration resulted in a marked decrease in the levels of PREG, DHEA, AP, PREGS, DHEAS (P<0.05) in male rat nucleus accumbens,and also AP, PREGS(P<0.05) in amygdala; ethanol withdrawal(6 h) induced a significant decrease in the concentration of DHEA, DHEAS, PREGS in nucleus accumbens (P<0.05)and PREGS in amygdala (P<0.05); ethanol withdrawal(24 h) increased significantly the DHEA levels in amygdala (P<0.05), and decreased the levels of DHEAS,PREGS in nucleus accumbens and amygdala (P<0.01). Conclusion: Ethanol dependence and withdrawal have different effect on the neurosteroids in rat nucleus accumbens and amygdala which might be involved in the development of ethanol dependence.