Reduced d-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA receptor-dependent synaptic plasticity
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Cocaine seeking behaviour and relapse have been linked to impaired potentiation and depression at excitatory synapses in the nucleus accumbens, but the mechanism underlying this process is poorly understood. We show that, in the rat nucleus accumbens core, D-serine is the endogenous coagonist of N-methyl-D-aspartate receptors, and its presence is essential for N-methyl-D-aspartate receptor-dependent potentiation and depression of synaptic transmission. Nucleus accumbens core slices obtained from cocaine-treated rats after 1 day of abstinence presented significantly reduced D-serine concentrations, increased expression of the D-serine degrading enzyme, D-amino acid oxidase, and downregulated expression of serine racemase, the enzyme responsible for D-serine synthesis. The D-serine deficit was associated with impairment of potentiation and depression of glutamatergic synaptic transmission, which was restored by slice perfusion with exogenous D-serine. Furthermore, in vivo administration of D-serine directly into the nucleus accumbens core blocked behavioural sensitization to cocaine. These results provide evidence for a critical role of D-serine signalling in synaptic plasticity relevant to cocaine addiction.
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Exogenous D-serine treatment reverts impaired plasticity and reduces behavioral manifestations associated with cocaine addiction, including cocaine-induced place preference, reinstatement of cocaine self-administration, and locomotor sensitization to cocaine.
“In keeping, exogenous D-serine treatment reverts the impaired plasticity and reduces a number of behavioral manifestations associated to cocaine addiction, including cocaine-induced place preference 121, 122 , reinstatement of cocaine self-administration (relapse) 123 and locomotor sensitization to cocaine 120, 121 .”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [120]
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- Authors
- Curcio, L., Podda, M. V., Leone, L., Piacentini, R., Mastrodonato, A., Cappelletti, P., Sacchi, S., Pollegioni, L., Grassi, C., & D’Ascenzo, M.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- University of Insubria (IT)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-03-20
- Volume
- 136
- Issue
- 4
- Pages
- 1216-1230
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2150417149
- Cited by
- 79
- References
- 58
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 12 · 2015: 7 · 2014: 9 · 2013: 3
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Funders
- Istituto Italiano di Tecnologia
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- D-serine, nucleus accumbens, cocaine, NMDA receptor, synaptic plasticity, synaptic potentiation, synaptic depression, D-amino acid oxidase, serine racemase, glutamatergic neurotransmission, behavioral sensitization, cocaine dependence, cocaine abstinence
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Male, Synaptic Transmission, Neuronal Plasticity, Nucleus Accumbens, Serine, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Equidae, Mice, Rats
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