Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
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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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Calcium-permeable, GluA2-lacking AMPARs appear after a dose of an addictive drug.
“Calcium-permeable, GluA2-lacking AMPARs appear (Bellone and Lu ¨scher 2006), while NMDAR function is decreased.”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Bellone and Lüscher 2006
NMDAR function is decreased after a dose of an addictive drug.
“Calcium-permeable, GluA2-lacking AMPARs appear (Bellone and Lu ¨scher 2006), while NMDAR function is decreased.”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Bellone and Lüscher 2006
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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
- Licence
- 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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