Extinction of morphine-dependent conditioned behavior is associated with increased phosphorylation of the GluR1 subunit of AMPA receptors at hippocampal synapses.
Extinction of morphine-dependent conditioned behavior is associated with increased phosphorylation of the GluR1 subunit of AMPA receptors at hippocampal synapses.
复制标题
DOI：
10.1111/j.1460-9568.2008.06560.x
复制
发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Morón JA
中科院分区：
文献类型：
--
作者：
Billa SK;Sinha N;Rudrabhatla SR;Morón JA
在戒断性阿片成瘾者中，与药物使用有关的环境线索可能会引发复发；因此，破坏这些习得的联系可能是减少复发的有效方法。有趣的是，谷氨酸能系统被认为与阿片剂诱导的行为可塑性有关。在这项研究中，研究了对阿片类药物配对的环境表现出条件性反应的大鼠以及这种条件性行为消失的动物海马区AMPA谷氨酸受体亚单位(GluR1，GluR2)表达和磷酸化水平的变化。此外，另一组动物接受了药物不配对的范例(没有条件作用)，以检查药物本身的药理学效果。用亚细胞分裂技术分析突触内AMPA谷氨酸亚基的局部分布，特别是突触后密度(PSD)。结果表明，吗啡依赖的条件性反应不改变GluR1或GluR2的表达或重新分布；然而，不成对的吗啡给药导致突触外部位GluR1亚单位的磷酸化增加。有趣的是，条件性反应的消退显著增加了PSD处GluR1亚单位的磷酸化。因此，我们认为，在突触内，PSD处GluR1亚单位的磷酸化可能是阿片类药物相关条件反应消退的关键机制。
In abstinent opiate addicts, relapse can be triggered by exposure to environmental cues associated with drug use; thus, the disruption of these learned associations may be an effective approach for reducing relapse. Interestingly, glutamatergic systems are thought to be involved in opiate-induced behavioral plasticity. In this study, changes in expression and phosphorylation levels of AMPA glutamate receptor subunits (GluR1, GluR2) in the hippocampus were investigated in rats showing a conditioned response to an opiate-paired environment as well as in animals in which this conditioned behavior was extinguished. Additionally, another set of animals went through a drug-unpaired paradigm (without conditioning) in order to examine the effects of the pharmacology of the drug itself. Subcellular fractionation techniques were used to analyze the local distribution of AMPA glutamate subunits within the synapse, especially at the postsynaptic density (PSD). Results showed that morphine-dependent conditioned responses did not alter expression or redistribution of GluR1 or GluR2; however the unpaired administration of morphine resulted in an increase in the phosphorylation of the GluR1 subunit at extrasynaptic sites. Interestingly, the extinction of the conditioned response significantly increased phosphorylation of the GluR1 subunit at the PSD. Therefore we propose that, within the synapse, the phosphorylation of the GluR1 subunit at the PSD may be a key mechanism in the extinction of opiate-associated conditioned responses.
登录
查看更多内容
影响因子：
10.6
作者：
Lattal, K. Matthew;Radulovic, Jelena;Lukowiak, Ken
通讯作者：
Lukowiak, Ken
影响因子：
16.2
作者：
Ehlers, MD
通讯作者：
Ehlers, MD
吗啡调节小鼠海马 CA1 区谷氨酸的释放。
影响因子：
2.5
作者：
Guo, M;Xu, NH;Pei, G
通讯作者：
Pei, G
影响因子：
3.3
作者：
Harris, GC;Wimmer, M;Aston-Jones, G
通讯作者：
Aston-Jones, G
影响因子：
5
作者：
Biala, Grazyna;Budzynska, Barbara
通讯作者：
Budzynska, Barbara