Cited by 79Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

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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Curcio, Livia, Podda, Maria V., Leone, Lucia, Piacentini, Roberto, Mastrodonato, Alessia, Cappelletti, Pamela, Sacchi, Silvia, Pollegioni, Loredano +2 more·2013·Brain

Abstract

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 .”

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  1. Bendikov I, Nadri C, Amar S, Panizzutti R, De Miranda J, Wolosker H, et al. ACSF and postmortem brain study of D-serine metabolic param- eters in schizophrenia. Schizophr Res 2007; 90: 41-51.

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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)
Venue
Brain
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
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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