Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation.
Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation.
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DOI：
10.1371/journal.pone.0015870
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发表时间：
2010-12-31
期刊：
影响因子：
3.7
通讯作者：
Lüscher C
中科院分区：
文献类型：
--
作者：
Brown MT;Bellone C;Mameli M;Labouèbe G;Bocklisch C;Balland B;Dahan L;Luján R;Deisseroth K;Lüscher C
Addictive drugs have in common that they cause surges in dopamine (DA) concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA). Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs) at glutamatergic synapes in DA neurons. However it remains elusive which molecular target of cocaine drives such AMPAR redistribution and whether other addictive drugs (morphine and nicotine) cause similar changes through their effects on the mesolimbic DA system. We used in vitro electrophysiological techniques in wild-type and transgenic mice to observe the modulation of excitatory inputs onto DA neurons by addictive drugs. To observe AMPAR redistribution, post-embedding immunohistochemistry for GluA2 AMPAR subunit was combined with electron microscopy. We also used a double-floxed AAV virus expressing channelrhodopsin together with a DAT Cre mouse line to selectively express ChR2 in VTA DA neurons. We find that in mice where the effect of cocaine on the dopamine transporter (DAT) is specifically blocked, AMPAR redistribution was absent following administration of the drug. Furthermore, addictive drugs known to increase dopamine levels cause a similar AMPAR redistribution. Finally, activating DA VTA neurons optogenetically is sufficient to drive insertion of GluA2-lacking AMPARs, mimicking the changes observed after a single injection of morphine, nicotine or cocaine. We propose the mesolimbic dopamine system as a point of convergence at which addictive drugs can alter neural circuits. We also show that direct activation of DA neurons is sufficient to drive AMPAR redistribution, which may be a mechanism associated with early steps of non-substance related addictions.
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影响因子：
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作者：
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DOI：
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