Bidirectional Modulation of Incubation of Cocaine Craving by Silent Synapse-Based Remodeling of Prefrontal Cortex to Accumbens Projections
Open accessAbstract
Glutamatergic projections from the medial prefrontal cortex (mPFC) to nucleus accumbens (NAc) contribute to cocaine relapse. Here we show that silent synapse-based remodeling of the two major mPFC-to-NAc projections differentially regulated the progressive increase in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Specifically, cocaine self-administration in rats generated AMPA receptor-silent glutamatergic synapses within both infralimbic (IL) and prelimbic mPFC (PrL) to NAc projections, measured after 1 day of withdrawal. After 45 days of withdrawal, IL-to-NAc silent synapses became unsilenced/matured by recruiting calcium-permeable (CP) AMPARs, whereas PrL-to-NAc silent synapses matured by recruiting non-CP-AMPARs, resulting in differential remodeling of these projections. Optogenetic reversal of silent synapse-based remodeling of IL-to-NAc and PrL-to-NAc projections potentiated and inhibited, respectively, incubation of cocaine craving on withdrawal day 45. Thus, pro- and antirelapse circuitry remodeling is induced in parallel after cocaine self-administration. These results may provide substrates for utilizing endogenous antirelapse mechanisms to reduce cocaine relapse.
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Weakening inputs to the nucleus accumbens can reverse previously established reward responses to addictive drugs.
“Conversely, weakening inputs to the NAc can reverse previously established reward responses to addictive drugs [231,232].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [231]
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References 57 · Cited by 344
- Authors
- Ma, Y.-Y., Lee, B. R., Wang, X., Guo, C., Liu, L., Cui, R., Lan, Y., Balcita-Pedicino, J. J., Wolf, M. E., Sesack, S. R., Shaham, Y., Schlüter, O. M., Huang, Y. H., & Dong, Y.
- Affiliations
- University of Pittsburgh (US)
- Allen Institute for Brain Science (US)
- Northeast Normal University (CN)
- Rosalind Franklin University of Medicine and Science (US)
- National Institute on Drug Abuse (US)
- European Neuroscience Institute Göttingen (DE)
- Corresponding author
- Huang, Yanhua H.
- Dong, Yan
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 83
- Issue
- 6
- Pages
- 1453-1467
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4295617
- OpenAlex
- W2047783720
- Cited by
- 344
- References
- 57
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 24 · 2023: 18 · 2022: 26 · 2021: 34 · 2020: 30 · 2019: 31 · 2018: 41 · 2017: 33 · 2016: 33 · 2015: 32 · 2014: 5
- FWCI
- 15.68
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-12-17)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH101147, MH101147)
- National Institute on Drug Abuse (DA009621, R01DA030379, R01DA023206, DA029565, K99DA029565, DA034856, DA015835, DA035805, DA028020, R01DA015835, R01DA035805, R00DA029565, DA023206, R01DA034856, DA030379, R37DA015835, F31DA028020, R01DA009621, R37DA023206)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cocaine craving, cocaine relapse, silent synapses, calcium-permeable AMPA receptors, medial prefrontal cortex, nucleus accumbens, infralimbic cortex, prelimbic cortex, glutamatergic synapses, cocaine withdrawal, synaptic remodeling
- MeSH terms
- Animals, Electrophysiology, Male, Neural Pathways, Neuronal Plasticity, Nucleus Accumbens, Synapses, Rats, Sprague-Dawley, Prefrontal Cortex, Cocaine-Related Disorders, Rats, Drug-Seeking Behavior, Optogenetics, Craving
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