孕酮对大鼠吗啡奖赏效应及下丘脑和纹状体内单胺递质水平的影响

目的:观察孕酮对于吗啡所致奖赏效应及下丘脑、纹状体内单胺类神经递质水平的影响。方法:采用大鼠条件性位置偏爱(CPP)模型,建立离体电化学检测技术高效液相色谱法测定大鼠下丘脑及纹状体内去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的含量。结果:吗啡(5mg·kg-1)可诱导大鼠产生稳定的CPP效应;孕酮(5mg·kg-1及20mg·kg-1)本身不产生CPP效应,但能抑制吗啡诱导的CPP效应。与对照组比较,吗啡诱导CPP形成时,下丘脑内NE水平明显升高(P<0.05),纹状体内NE、DA和HT的水平明显升高(P<0.05,P<0.01)。与吗啡组比较,合用20mg·kg-1孕酮使纹状体内DA水平显著下降(P<0.01)。结论:孕酮对吗啡的CPP效应具有一定的抑制作用,其机制可能与降低纹状体内DA水平有关。

EFFECT OF PROGESTERONE ON MORPHINE -INDUCED REWARD AND THE LEVELS OF MONOAMINE TRANSMITTERS IN RAT HYPOTHALAMUS AND STRIATUM

Objective:To study the effect of progesterone on morphine-induced reward and its relation to monoamine transmitter level in rat hypothalamus (Ht) and striatum (Str). Methods:Conditioned place preference (CPP) test was used to investigate the morphine rewarding effects, and high-performance liquid chromatography with electrochemical detection (HPLC-ECD) was established to determine the levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in rat Str and Ht. Results:Morphine 5 mg·kg~ -1 could successfully induce the formation of CPP. Progesterone (5 mg·kg~ -1 and 20 mg·kg~ -1 )could not induce CPP itself, but was able to abolish the morphine-induced CPP. Compared with control group, the significant increases of NE content in Ht (P<0.05) , NE, DA and HT contents in Str (P<0.05, P<0.01) following morphine administration were demonstrated. Compared with morphine group, the increase of DA level in Str by morphine could be attenuated by co-administering 20 mg·kg~ -1 progesterone (P<0.01). Conclusion:It is speculated that progesterone may effectively attenuate morphine-induced CPP. Neurochemical analysis reveals that the effect of progesterone can be related to down-regulating the level of DA in rat Str.