Neonatal Prefrontal Inactivation Results in Reversed Dopaminergic Responses in the Shell Subregion of the Nucleus Accumbens to NMDA Antagonists

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• 作者：Tiphaine Pouvreau ; Emmanuelle Tagliabue ; Yusuf Usun ; Séverine Eybrard ; Francisca Meyer ; Alain Louilot
• 刊名：ACS Chemical Neuroscience
• 出版年：2016
• 出版时间：July 20, 2016
• 年：2016
• 卷：7
• 期：7
• 页码：964-971
• 全文大小：460K
• 年卷期：0
• ISSN：1948-7193

文摘

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.