Cited by 430Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

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

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Bellone, Camilla, Lüscher, Christian·2006·Nature Neuroscience

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.

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Crossref · 10.1038/nn1682

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Authors
Bellone, C., & Lüscher, C.
Affiliations
University of Geneva (CH)
Corresponding author
Lüscher, Christian
Venue
Nature Neuroscience
Published
2006-04-02
Volume
9
Issue
5
Pages
636-641
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2042529649
Cited by
429
References
51
Citations by year
2026: 6 · 2025: 5 · 2024: 16 · 2023: 8 · 2022: 21 · 2021: 19 · 2020: 11 · 2019: 15 · 2018: 25 · 2017: 19 · 2016: 28 · 2015: 17 · 2014: 22 · 2013: 34 · 2012: 31
FWCI
10.44
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
cocaine, metabotropic glutamate receptor 1, long-term depression, depotentiation, ventral tegmental area, dopaminergic neurons, GluR2, PICK1, synaptic plasticity, addiction, glutamatergic synapses, joro spider toxin
MeSH terms
Animals, Animals, Newborn, Carrier Proteins, Cocaine, Dose-Response Relationship, Radiation, Drug Interactions, Electric Stimulation, Enzyme Inhibitors, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Synaptic Transmission, Neurons, Nuclear Proteins, Ventral Tegmental Area, Receptors, AMPA, Receptors, Metabotropic Glutamate, Patch-Clamp Techniques, Dopamine Antagonists, Statistics, Nonparametric, Dopamine Uptake Inhibitors, Cell Cycle Proteins, Excitatory Postsynaptic Potentials, Long-Term Synaptic Depression, Mice, In Vitro Techniques

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