Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
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DOI：
10.1038/nn1682
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发表时间：
2006-05-01
影响因子：
25
通讯作者：
Lüscher, C
中科院分区：
文献类型：
--
作者：
Bellone, C;Lüscher, C
滥用药物会引起神经回路的长期变化，而这些变化可能是成瘾核心组成部分的基础。在这里，我们专注于多巴胺（DA）神经元的腹侧被盖区（VTA）的多巴胺能突触。使用“离体”的方法在小鼠中，我们表明，单次注射可卡因引起强烈的整流和赋予的敏感性多胺Joro蜘蛛毒素（JST）的AMPAR介导的兴奋性突触后电流（AMPAR EPSC），表明缺乏GluR 2的受体的招聘。这种传输的质的变化被AMPAR：NMDAR比率的增加所抑制，并且通过干扰与体内C激酶-1（PICK 1）相互作用的蛋白质而被阻止。代谢型谷氨酸受体（mGluR 1 s）通过腹膜内注射的阳性调节剂去增强突触和可卡因处理的小鼠切片取消整流激活，揭示了体内逆转可卡因诱导的突触可塑性的机制。
Drugs of abuse induce long-lasting changes in neural circuits that may underlie core components of addiction. Here we focus on glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area (VTA). Using an 'ex vivo' approach in mice, we show that a single injection of cocaine caused strong rectification and conferred sensitivity to the polyamine Joro spider toxin (JST) of AMPAR-mediated excitatory postsynaptic currents (AMPAR EPSCs), indicating the recruitment of receptors that lack GluR2. This qualitative change in transmission was paralleled by an increase in the AMPAR: NMDAR ratio and was prevented by interfering with the protein interacting with C kinase-1 (PICK1) in vivo. Activation of metabotropic glutamate receptors (mGluR1s) by intraperitoneal injection of a positive modulator depotentiated synapses and abolished rectification in slices of cocaine-treated mice, revealing a mechanism to reverse cocaine-induced synaptic plasticity in vivo.