胍丁胺对吗啡长期处理引起的NMDA受体蛋白表达改变的影响

目的:观察胍丁胺对吗啡长期处理引起的NMDA受体蛋白改变的影响。方法:采用吗啡递增给药制备大鼠慢性依赖模型,并观察依赖状态下大鼠海马和伏隔核NMDA受体NR1和NR2B亚基蛋白表达量的变化,以及胍丁胺对吗啡作用的影响。结果:与对照组相比,吗啡慢性处理大鼠在纳洛酮催促下能出现典型的戒断综合征,提示依赖模型建立成功。用免疫印记(Western blotting)技术发现,海马部位的NR2B亚基明显下调,而NR1亚基未见显著性变化;吗啡慢性处理不引起伏隔核NR2B亚基的明显变化,但NR1亚基却显著上调。胍丁胺与吗啡伴随给药能逆转吗啡对两脑区NMDA受体蛋白表达的调节作用。结论:胍丁胺调节阿片依赖可能与其逆转吗啡对NMDA受体亚基数量和构成的调节有关。

REGULATION OF AGMATINE ON NMDA RECEPTORS EXPRESSION IN MORPHINE DEPENDENT RATS

Objective:To investigatethe influence of agmatine on NMDA receptors′expressionunder long-term treatment of morphine. Methods:A model of chronic morphine dependence was established by repeated administration of morphine with progressive doses.Western blotting was used to examine the changes of NMDA receptors′(NR1 and NR2B subunits) expression and the influence of agmatine on morphine′s effect in hippocampus and nucleus accumbensof morphine-dependent rats.Results:Compared with control, a typical behavioral abstinence syndrome of the rats precipitatedby naloxoneindicatedasuccessful establishment ofdependent model.The NR2B subunit was down-regulated significantlyat hippocampus in morphine-dependent rats, while the NR1 subunit was not changed. This suggests the construction of NMDA receptors bealtered. And the NR2B subunit had no change but NR1 subunit was up-regulated at nucleus accumbens, suggesting the level of NMDA receptors be changed. Agmatine co-treated with morphine could reversemorphine′s regulation on NMDA receptors′expression in these two regions. Conclusion:The mechanism of regulation of agmatine on opioid dependence is related to the reverse effect on the NMDA receptors′level and construction.