UNIGE document Scientific Article
previous document  unige:10184  next document
add to browser collection
Title

Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression

Authors
Published in Nature Neuroscience. 2006, vol. 9, no. 5, p. 636-641
Abstract 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.
Keywords AnimalsAnimals, NewbornCarrier Proteins/pharmacologyCocaine/ pharmacologyDopamine Antagonists/pharmacologyDopamine Uptake Inhibitors/ pharmacologyDose-Response Relationship, RadiationDrug InteractionsElectric Stimulation/methodsEnzyme Inhibitors/pharmacologyExcitatory Postsynaptic Potentials/drug effectsLong-Term Synaptic Depression/ drug effectsMethoxyhydroxyphenylglycol/analogs & derivatives/pharmacologyMiceMice, Inbred C57BLNeurons/ drug effectsNuclear Proteins/pharmacologyPatch-Clamp Techniques/methodsReceptors, AMPA/ metabolismReceptors, Metabotropic Glutamate/ metabolismStatistics, NonparametricSynaptic Transmission/drug effectsVentral Tegmental Area/cytology
Stable URL http://archive-ouverte.unige.ch/unige:10184
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www.nature.com/neuro/journal/v9/n5/abs/nn1682.html
Identifiers
PMID: 16582902
Structures
136 hits and 0 download since 2010-08-06
Update
Export document
Format :
Citation style :