Nature Neuroscience 9, 636 - 641 (2006)
Published online: 2 April 2006; | doi:10.1038/nn1682
Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depressionCamilla Bellone1
& Christian Lüscher1, 21
Department of Basic Neurosciences, University of Geneva, 1 Michel Servet, CH-1211 Geneva, Switzerland. 2
Clinic of Neurology, University of Geneva, 1 Michel Servet, CH-1211 Geneva, Switzerland.
Correspondence should be addressed to Christian Lüscher Christian.Luscher@medecine.unige.ch 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.
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