Chronic morphine treatment alters expression of N-methyl-D-aspartate receptor subunits in the extended amygdala
Chronic morphine treatment alters expression of N-methyl-D-aspartate receptor subunits in the extended amygdala
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DOI：
10.1002/jnr.20756
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发表时间：
2006-03-01
影响因子：
4.2
通讯作者：
Siggins, GR
中科院分区：
文献类型：
--
作者：
Bajo, M;Crawford, EF;Siggins, GR
杏仁核（NAcc）和中央杏仁核（CeA）是扩展杏仁核的一部分，扩展杏仁核是一种在药物滥用和依赖中起关键作用的复合体。我们以前的研究表明，阿片类药物和乙醇改变了这些区域的多巴胺能传递。N-甲基-D-天冬氨酸（NMDA）受体是阿片能传递的关键成分，可能参与阿片耐受和依赖的形成。在这项研究中，我们研究了慢性吗啡给药对NAcc和CeA中三种主要NMDA受体亚基（NR 1，NR 2A和NR 2B）基因和蛋白表达的影响。实时荧光定量PCR显示，在整个NAcc的任何亚基的mRNA水平之间的幼稚和吗啡依赖的大鼠没有差异。然而，在蛋白质水平，免疫印迹显示，慢性吗啡显着增加NRII和NR 2B亚基的水平。与NAcc的情况相反，在CeA中，我们发现吗啡依赖大鼠中NR 1亚基的mRNA水平增加，但所有三个亚基的蛋白水平不变。吗啡依赖大鼠NMDA受体亚单位表达的改变，特别是在NAcc中，可能代表了对慢性吗啡的神经适应，并提出了依赖大鼠延伸杏仁核中发现的多巴胺能传递变化的机制。此外，我们的研究结果表明，在基因和蛋白质水平的区域特异性反应的NMDA受体亚基慢性吗啡给药。(C)2006 Wiley-Liss，Inc.
The nucleus accumbens (NAcc) and central amygdala (CeA) are parts of the extended amygdala, a complex that plays a key role in drug abuse and dependence. Our previous studies showed that opiates and ethanol alter glutamatergic transmission in these regions. N-methyl-D-aspartate (NMDA) receptors are key components of glutamatergic transmission likely involved in the development of opiate tolerance and dependence. In this study we examined the effects of chronic morphine administration on gene and protein expression of three major NMDA receptors subunits (NR1, NR2A, and NR2B) in NAcc and CeA. Real-time PCR showed no differences in mRNA levels of any of the subunits in the whole NAcc between naive and morphine-dependent rats. However, at the protein level, immunoblotting revealed that chronic morphine significantly increased levels of NRII and NR2B subunits. In contrast to the case for NAcc, in CeA we found an increased mRNA level for the NR1 subunit only but unchanged protein levels of all three subunits in morphine-dependent rats. The altered expressions of NMDA receptor subunits, especially in NAcc, of morphine-dependent rats may represent a neuroadaptation to chronic morphine and suggest a mechanism for the changes of glutamatergic transmission found in the extended amygdala in dependent rats. In addition, our results indicate a region-specific response of NMDA receptor subunits to chronic morphine administration at the gene and protein levels. (C) 2006 Wiley-Liss, Inc.