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

• DOI: 10.1093/brain/awt036
• Publication Date: 2013-03-22T00:37:27Z
• Authors: Livia Curcio; Maria V. Podda; Lucia Leone; Roberto Piacentini; Alessia Mastrodonato; Pamela Cappelletti; Silvia Sacchi; Loredano Pollegioni; Claudio Grassi; Marcello D’Ascenzo
• Keywords: Male; 0301 basic medicine; synaptic plasticity; Neuronal Plasticity; Behavior, Animal; nucleus accumbens; cocaine; D-serine; Equidae; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Nucleus Accumbens; Rats; Mice; 03 medical and health sciences; Cocaine; Animals, Behavior; Animal; drug effects, Cocaine; pharmacology, Equidae, Male, Mice, Neuronal Plasticity; drug effects, Nucleus Accumbens; metabolism/pathology/ultrastructure, Rats, Rats; Wistar, Receptors; N-Methyl-D-Aspartate; agonists/metabolism, Serine; antagonists /&/ inhibitors/metabolism/pharmacology, Synaptic Transmission; drug effects; Serine; Animals; Rats, Wistar

Cocaine seeking behaviour and relapse have been linked to impaired potentiation depression at excitatory synapses in the nucleus accumbens, but mechanism underlying this process is poorly understood. We show that, rat accumbens core, d-serine endogenous coagonist of N-methyl-d-aspartate receptors, its presence essential for receptor-dependent synaptic transmission. Nucleus core slices obtained from cocaine-treated rats after 1 day abstinence presented significantly reduced concentrations, increased expression degrading enzyme, d-amino acid oxidase, downregulated serine racemase, enzyme responsible synthesis. The deficit was associated with impairment glutamatergic transmission, which restored by slice perfusion exogenous d-serine. Furthermore, vivo administration directly into blocked behavioural sensitization cocaine. These results provide evidence a critical role signalling plasticity relevant cocaine addiction.