吗啡依赖大鼠纹状体内神经甾体水平的变化

目的:探讨吗啡躯体依赖、精神依赖和戒断对♂大鼠纹状体内神经甾体水平的影响。方法:高效液相色谱-质谱法测定大鼠纹状体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:(1)与纳洛酮对照组比较,纳洛酮催促吗啡戒断大鼠的纹状体内PREG的含量显著升高(P<0.01);血浆中PREG、AP、DHEAS和PREGS的含量显著升高(P<0.01),而DHEA的含量显著降低(P<0.01);(2)与生理盐水对照组比较,吗啡精神依赖大鼠的纹状体内DHEA和PREG的含量显著升高(P<0.01),血浆中DHEA的水平显著降低(P<0.01)。结论:慢性吗啡处理可影响大鼠纹状体内某些神经甾体的水平,表明神经甾体可能参与吗啡依赖的形成。

CHANGES OF NEUROSTEROID LEVELS IN THE STRIATUM OF MORPHINE DEPENDENT MALE RATS

Objective:To determine if chronic morphine abuse elicits neurosteroid level alterations in male rat striatum.Methods:Striatum tissue and plasma were collected and analyzed for neurosteroid concentrations using liquid chromatography-negative atmospheric pressure ionization mass spectrometry(HPLC-MS). Results:(1)Compared with naloxone-control group,naloxone-induced morphine withdrawal elevated pregnenolone(PREG) level in rat striatum(P<0.01),elevated PREG,allopregnanolone(AP),dehydroepiandrosterone sulfate(DHEAS) and pregnenolone sulfate(PREGS) levels in rat plasma(P<0.01),while decreased dehydroepiandroster-(one(DHEA)) content in rat plasma(P<0.01);(2)Compared with saline control,morphine-induced conditioned place preference elevated DHEA and PREG contents in rat striatum(P<0.01),while decreased DHEA level in rat plasma(P<0.01).Conclusion: Chronic morphine treatment and naloxone-induced morphine withdrawal affect neurosteroid levels in rat striatum and/or plasma,which suggests that endogenous neurosteroids may be related to the development of morphine dependence.