D-amino acid oxidase is expressed in the ventral tegmental area and modulates cortical dopamine
Abstract
D-amino acid oxidase (DAO, DAAO) degrades the NMDA receptor co-agonist D-serine, modulating D-serine levels and thence NMDA receptor function. DAO inhibitors are under development as a therapy for schizophrenia, a disorder involving both NMDA receptor and dopaminergic dysfunction. However, a direct role for DAO in dopamine regulation has not been demonstrated. Here, we address this question in two ways. First, using in situ hybridization and immunohistochemistry, we show that DAO mRNA and immunoreactivity are present in the ventral tegmental area (VTA) of the rat, in tyrosine hydroxylase (TH)-positive and -negative neurons, and in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Second, we show that injection into the VTA of sodium benzoate, a DAO inhibitor, increases frontal cortex extracellular dopamine, as measured by in vivo microdialysis and high performance liquid chromatography. Combining sodium benzoate and D-serine did not enhance this effect, and injection of D-serine alone affected dopamine metabolites but not dopamine. These data show that DAO is expressed in the VTA, and suggest that it impacts on the mesocortical dopamine system. The mechanism by which the observed effects occur, and the implications of these findings for schizophrenia therapy, require further study.
Citation
Betts , J F , Schweimer , J V , Burnham , K E , Burnet , P W J , Sharp , T & Harrison , P J 2014 , ' D-amino acid oxidase is expressed in the ventral tegmental area and modulates cortical dopamine ' , Frontiers in Synaptic Neuroscience , vol. 6 , 11 . https://doi.org/10.3389/fnsyn.2014.00011
Publication
Frontiers in Synaptic Neuroscience
Status
Peer reviewed
ISSN
1663-3563Type
Journal article
Rights
Copyright © 2014 Betts, Schweimer, Burnham, Burnet, Sharp and Harrison. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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