title: Neonatal Prefrontal Inactivation Results in Reversed Dopaminergic Responses in the Shell Subregion of the Nucleus Accumbens to NMDA Antagonists.
abstract: Striatal dopaminergic dysregulation in schizophrenia could result from a prefronto-striatal dysconnectivity, of neurodevelopmental origin, involving N-methyl-d-aspartate (NMDA) receptors. The dorsomedian shell part of the nucleus accumbens is a striatal subregion of particular interest inasmuch as it has been described as the common target region for antipsychotics. Moreover, NMDA receptors located on the dopaminergic endings have been reported in the shell. The present study examines in adult rats the effects of early functional inactivation of the left prefrontal cortex on behavioral and dopaminergic responses in the dorsomedian shell part of the nucleus accumbens following administration of two noncompetitive NMDA receptor antagonists, ketamine, and dizocilpine (MK-801). The results showed that postnatal blockade of the prefrontal cortex led to increased locomotor activity as well as increased extracellular dopamine levels in the dorsomedian shell following administration of both noncompetitive NMDA receptor antagonists, and, more markedly, after treatment with the more specific one, MK-801, whereas decreased dopaminergic levels were observed in respective controls. These data suggest a link between NMDA receptor dysfunctioning and dopamine dysregulation at the level of the dorsomedian shell part of the nucleus accumbens. They may help to understand the pathophysiology of schizophrenia in a neurodevelopmental perspective.
authors.affiliation: INSERM U 1114, Faculty of Medicine, FMTS, University of Strasbourg, Strasbourg 67085, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Pouvreau
authors.affiliation: INSERM U 1114, Faculty of Medicine, FMTS, University of Strasbourg, Strasbourg 67085, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Tagliabue
authors.affiliation: INSERM U 1114, Faculty of Medicine, FMTS, University of Strasbourg, Strasbourg 67085, France.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Usun
authors.affiliation: INSERM U 1114, Faculty of Medicine, FMTS, University of Strasbourg, Strasbourg 67085, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Eybrard
authors.affiliation: Department of Molecular Animal Physiology, Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Francisca
authors.initials: F
authors.lastname: Meyer
authors.affiliation: INSERM U 1114, Faculty of Medicine, FMTS, University of Strasbourg, Strasbourg 67085, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Louilot
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D013779:Tetrodotoxin; D007649:Ketamine; D016291:Dizocilpine Maleate; D004298:Dopamine
keywords: Ketamine; MK-801; TTX; animal modeling; in vivo voltammetry; schizophrenia