Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area
Open accessAbstract
The manner in which drug-evoked synaptic plasticity affects reward circuits remains largely elusive. We found that cocaine reduced NMDA receptor excitatory postsynaptic currents and inserted GluA2-lacking AMPA receptors in dopamine neurons of mice. Consequently, a stimulation protocol pairing glutamate release with hyperpolarizing current injections further strengthened synapses after cocaine treatment. Our data suggest that early cocaine-evoked plasticity in the ventral tegmental area inverts the rules for activity-dependent plasticity, eventually leading to addictive behavior.
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A common protocol to test the NMDAR/AMPAR ratio in response to the synaptic release of glutamate is to measure the ratio of the evoked excitatory postsynaptic current when the NMDAR is blocked by holding the cell at −70 mV to obtain a pure AMPAR component versus when the cell is held at +40 mV to get a mixed AMPAR + NMDAR component.
“Therefore, a common protocol to test the NMDAR/AMPAR ratio in response to the synaptic release of glutamate is to measure the ratio of the evoked excitatory postsynaptic current when the NMDAR is blocked by holding the cell at −70 mV to obtain a pure AMPAR component versus when the cell is held at +40 mV to get a mixed AMPAR + NMDAR component (Figure 8d).22,23”
From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [23]
The presence of these receptors changes the rules for the induction of plasticity and mediates in vivo synaptic scaling.
“Furthermore, the presence of these receptors changes the rules for the induction of plasticity (Mameli et al., 2011) and mediates in vivo synaptic scaling (Garcia-Bereguiain et al., 2013).”
From Oxytocin neurons mediate the effect of social isolation via the VTA circuits (2022) · cites this paper as Mameli et al., 2011
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- Authors
- Mameli, M., Bellone, C., Brown, M. T. C., & Lüscher, C.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Lüscher, Christian
- Venue
- Nature Neuroscience
- Published
- 2011-02-20
- Volume
- 14
- Issue
- 4
- Pages
- 414-416
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1976063610
- Cited by
- 177
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 12 · 2020: 8 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 14 · 2015: 14 · 2014: 12 · 2013: 18 · 2012: 22
- FWCI
- 9.00
- 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, ventral tegmental area, synaptic plasticity, NMDA receptor currents, calcium-permeable AMPA receptors, dopaminergic neurons, glutamatergic neurotransmission, activity-dependent plasticity, reward systems, addiction
- MeSH terms
- Animals, Cocaine, Disease Models, Animal, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Ventral Tegmental Area, Glutamic Acid, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Mice
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