Neuroadaptations in the cellular and postsynaptic group 1 metabotropic glutamate receptor mGluR5 and Homer proteins following extinction of cocaine self-administration.
Neuroadaptations in the cellular and postsynaptic group 1 metabotropic glutamate receptor mGluR5 and Homer proteins following extinction of cocaine self-administration.
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DOI：
10.1016/j.neulet.2008.12.028
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发表时间：
2009-03-13
影响因子：
2.5
通讯作者：
Mantsch JR
中科院分区：
文献类型：
--
作者：
Ghasemzadeh MB;Vasudevan P;Mueller C;Seubert C;Mantsch JR
本研究探讨了第1组代谢型谷氨酸受体mGluR 5和相关的突触后支架蛋白Homer 1b/c的行为可塑性的作用后，从可卡因自我管理的戒断治疗。大鼠自我施用可卡因或盐水14天，随后是戒断期，在戒断期期间，大鼠进行消退训练，留在其饲养笼中，或在没有消退的情况下置于自我施用室中。随后，组织水平和分布的蛋白质在突触体部分与突触后密度进行了检查。在笼舍暴露后进行的Coconut自身给药降低了延髓核（NA）壳和背外侧纹状体中的mGluR 5蛋白。而消退训练降低了NAshell、NAcore和背外侧纹状体的mGluR 5蛋白，但没有表现出任何变化。支架蛋白PSD 95在灭绝动物的NAcore中增加。寻求药物的灭绝与NAshell中突触体mGluR 5蛋白的显著减少和背外侧纹状体中的增加相关，而NAcore的未被修改。有趣的是，Homer 1b/c和PSD 95支架蛋白在NA壳而不是NA核中的消退训练后的突触体部分中减少。寻求药物的行为也与背外侧纹状体中mGluR 5受体和肌动蛋白的增加有关。因此，可卡因寻求的消失与mGluR 5表达和分布中的神经适应相关，这些神经适应是区域特异性的，包括可卡因诱导适应的抑制诱导逆转以及紧急抑制诱导的改变。支架蛋白的同时可塑性进一步表明，mGluR 5受体神经适应可能对突触功能有影响。
This study examined the role of group1 metabotropic glutamate receptor mGluR5 and associated postsynaptic scaffolding protein Homer1b/c in behavioral plasticity after three withdrawal treatments from cocaine self-administration. Rats self-administered cocaine or saline for 14 days followed by a withdrawal period during which rats underwent extinction training, remained in their home cages, or were placed in the self-administration chambers in the absence of extinction. Subsequently, the tissue level and distribution of proteins in the synaptosomal fraction associated with the postsynaptic density were examined. Cocaine self-administration followed by home cage exposure reduced the mGluR5 protein in nucleus accumbens (NA) shell and dorsolateral striatum. While extinction training reduced mGluR5 protein in NAshell, NAcore and dorsolateral striatum did not display any change. The scaffolding protein PSD95 increased in NAcore of the extinguished animals. Extinction of drug seeking was associated with a significant decrease in the synaptosomal mGluR5 protein in NAshell and an increase in dorsolateral striatum, while that of NAcore was not modified. Interestingly, both Homer1b/c and PSD95 scaffolding proteins were decreased in the synaptosomal fraction after extinction training in NAshell but not NAcore. Extinguished drug-seeking behavior was also associated with an increase in mGluR5 receptor and actin proteins in dorsolateral striatum. Therefore, extinction of cocaine seeking is associated with neuroadaptations in mGluR5 expression and distribution that are region-specific and consist of extinction-induced reversal of cocaine-induced adaptations as well as emergent extinction-induced alterations. Concurrent plasticity in the scaffolding proteins further suggests that mGluR5 receptor neuroadaptations may have implications for synaptic function.
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