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

Risultato della ricerca: Contributo in rivistaContributo a convegnopeer 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
Lingua originaleEnglish
pagine (da-a)118-118
Numero di pagine1
RivistaActa Physiologica
Volume206
Stato di pubblicazionePubblicato - 2012
EventoThe 63rd National Congress of the Italian Physiological Society - Verona
Durata: 21 set 201223 set 2012

Keywords

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

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