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  Prefrontal and striatal glutamate differently relate to striatal dopamine: Potential regulatory mechanisms of striatal presynaptic dopamine function?

Gleich, T., Deserno, L., Robert, L., Boehme, R., Pankow, A., Buchert, R., et al. (2015). Prefrontal and striatal glutamate differently relate to striatal dopamine: Potential regulatory mechanisms of striatal presynaptic dopamine function? The Journal of Neuroscience, 35(26), 9615-9621. doi:10.1523/JNEUROSCI.0329-15.2015.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-7E52-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-7BEF-7
Genre: Journal Article

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 Creators:
Gleich, Tobias1, 2, Author
Deserno, Lorenz1, 3, 4, Author              
Robert, Lorenz1, 5, Author
Boehme, Rebecca1, Author
Pankow, Anne1, Author
Buchert, Ralph6, Author
Kühn, Simone1, 7, Author
Heinz, Andreas1, Author
Schlagenhauf, Florian1, 4, Author              
Gallinat, Jürgen1, 8, Author
Affiliations:
1Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany, ou_persistent22              
2NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Germany, ou_persistent22              
3Department of Neurology, Charité University Medicine Berlin, Germany, ou_persistent22              
4Max Planck Fellow Group Cognitive and Affective Control of Behavioural Adaptation, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_1753350              
5Department of Psychology, Humboldt University Berlin, Germany, ou_persistent22              
6Department of Nuclear Medicine, Charité University Medicine Berlin, Germany, ou_persistent22              
7Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany, ou_persistent22              
8Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              

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Free keywords: Dopamine; FDOPA; PET; Glutamate; MRS; Prefrontal cortex; Striatum
 Abstract: Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18-l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity (n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity (n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity (n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia). SIGNIFICANCE STATEMENT The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role of prefrontal and striatal glutamate for ventral striatal presynaptic dopamine levels. Such glutamate–dopamine relationships improve our understanding of neurochemical interactions in prefrontostriatal circuits and have implications for the neurobiology of mental disease.

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Language(s): eng - English
 Dates: 2015-01-262015-05-212015-07-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1523/JNEUROSCI.0329-15.2015
PMID: 26134644
 Degree: -

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Title: The Journal of Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 35 (26) Sequence Number: - Start / End Page: 9615 - 9621 Identifier: ISSN: 0270-6474
CoNE: /journals/resource/954925502187