Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus Accumbens
Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus Accumbens
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DOI：
10.1523/jneurosci.2252-05.2005
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发表时间：
2005-10-05
影响因子：
5.3
通讯作者：
Wolf, ME
中科院分区：
文献类型：
--
作者：
Boudreau, AC;Wolf, ME
AMPA受体运输的调节对于许多形式的神经元可塑性是重要的。在这项研究中，使用蛋白质交联测定来评估AMPA受体运输对与行为敏化相关的可塑性的贡献，这是一种药物成瘾的动物模型。交联被用来区分细胞表面和细胞内AMPA受体在神经核（NAc）组织从大鼠反复处理盐水或可卡因。可卡因致敏大鼠末次注射后21 d谷氨酸受体1（GluR 1）和GluR 2/3亚基的表面/细胞内（S/I）比值增加，而未致敏大鼠则无此变化，可卡因致敏大鼠S/I比值的大小与行为致敏的大小呈正相关。在第1天戒断时间，可卡因没有改变S/I比值，S/I比值和行为敏感化之间没有相关性。大多数的表面表达的GluR 1检测与此测定与突触，基于与突触后密度蛋白的95 kDa的共免疫沉淀。这些研究结果表明，可卡因的行为敏化与AMPA受体的NAc神经元表面的缓慢发展的再分布有关。药物寻求反应的运动执行依赖于起源于皮层和边缘区的谷氨酸传入激活NAc神经元上的AMPA受体。我们认为可卡因致敏大鼠的觅药反应更有效，因为AMPA受体的细胞表面表达增加。
Regulation of AMPA receptor trafficking is important for many forms of neuronal plasticity. In this study, a protein cross- linking assay was used to evaluate the contribution of AMPA receptor trafficking to plasticity associated with behavioral sensitization, an animal model of drug addiction. Cross-linking was used to distinguish between cell surface and intracellular AMPA receptors in nucleus accumbens (NAc) tissue obtained from rats treated repeatedly with saline or cocaine. Surface/ intracellular (S/I) ratios for glutamate receptor 1 (GluR1) and GluR2/3 subunits were increased 21 d after the last injection in cocaine-sensitized rats but not rats that failed to sensitize, and the magnitude of the S/I ratio for cocaine-sensitized rats was positively correlated with the magnitude of behavioral sensitization. At the 1 d withdrawal time, cocaine did not alter S/I ratios, and there was no correlation between S/I ratios and behavioral sensitization. The majority of surface-expressed GluR1 detected with this assay was associated with synapses, based on coimmunoprecipitation with postsynaptic density protein of 95 kDa. These findings suggest that behavioral sensitization to cocaine is associated with a slowly developing redistribution of AMPA receptors to the surface of NAc neurons. Motor execution of drug-seeking responses depends on activation of AMPA receptors on NAc neurons by glutamate afferents originating in cortical and limbic regions. We propose that drug-seeking responses are more effectively triggered in cocaine-sensitized rats because of increased cell surface expression of AMPA receptors.