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Scientific article
English

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

Published inNature neuroscience, vol. 9, no. 5, p. 636-641
Publication date2006
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
  • Animals
  • Animals, Newborn
  • Carrier Proteins/pharmacology
  • Cocaine/ pharmacology
  • Dopamine Antagonists/pharmacology
  • Dopamine Uptake Inhibitors/ pharmacology
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation/methods
  • Enzyme Inhibitors/pharmacology
  • Excitatory Postsynaptic Potentials/drug effects
  • Long-Term Synaptic Depression/ drug effects
  • Methoxyhydroxyphenylglycol/analogs & derivatives/pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Neurons/ drug effects
  • Nuclear Proteins/pharmacology
  • Patch-Clamp Techniques/methods
  • Receptors, AMPA/ metabolism
  • Receptors, Metabotropic Glutamate/ metabolism
  • Statistics, Nonparametric
  • Synaptic Transmission/drug effects
  • Ventral Tegmental Area/cytology
Citation (ISO format)
BELLONE, Camilla, LUESCHER, Christian. Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression. In: Nature neuroscience, 2006, vol. 9, n° 5, p. 636–641. doi: 10.1038/nn1682
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ISSN of the journal1097-6256
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