title: Reduced D-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA receptor-dependent synaptic plasticity.
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.
authors.affiliation: Institute of Human Physiology, Medical School, Università Cattolica, 00168 Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Curcio
authors.forename: Maria V
authors.initials: MV
authors.lastname: Podda
authors.forename: Lucia
authors.initials: L
authors.lastname: Leone
authors.forename: Roberto
authors.initials: R
authors.lastname: Piacentini
authors.forename: Alessia
authors.initials: A
authors.lastname: Mastrodonato
authors.forename: Pamela
authors.initials: P
authors.lastname: Cappelletti
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacchi
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Ascenzo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D018397:Equidae; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D012694:Serine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D003042:Cocaine