Reduced D-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA-dependent synaptic plasticity

Lucia Leone, Maria Vittoria Podda, Roberto Piacentini, Claudio Grassi, Marcello D'Ascenzo, Livia Curcio, Pamela Cappelletti, Silvia Sacchi, Loredano Polleggioni

Research output: Contribution to journalConference articlepeer-review

Abstract

Cocaine seeking behavior and relapse have been linked to impaired potentiation and depression (LTP and LTD) at excitatory synapses in the nucleus accumbens (NAc), but the mechanism underlying this process is poorly understood. We show that, in the rat NAc core, D-serine is the endogenous coagonist of synaptic N-methyl D-aspartate receptors (NMDARs), and its presence is essential for NMDA-dependent LTP and LTD. NAc 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 LTP and LTD that was restored by slice perfusion with exogenous D-serine. Furthermore, in vivo administration of D-serine prevented behavioral sensitization to cocaine. These results provide evidence for a critical role of D-serine signaling in synaptic plasticity relevant to cocaine addiction
Original languageEnglish
Pages (from-to)118-118
Number of pages1
JournalActa Physiologica
Volume206
Publication statusPublished - 2012
EventThe 63rd National Congress of the Italian Physiological Society - Verona
Duration: 21 Sep 201223 Sep 2012

Keywords

  • D-serine
  • NMDA-receptor
  • Nucleus accumbens
  • synaptic plasticity

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