Prefrontal and striatal glutamate differently relate to striatal dopamine: Potential regulatory mechanisms of striatal presynaptic dopamine function?
Open accessAbstract
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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Neurochemical systems involved in fronto-striatal loops act in concerted and cross-regulatory fashions.
“and the neurochemical systems involved in fronto-striatal loops act in concerted and cross-regulatory fashions (Gleich et al., 2015).”
From The Interaction of Person-Affect-Cognition-Execution (I-PACE) model for addictive behaviors: Update, generalization to addictive behaviors beyond internet-use disorders, and specification of the process character of addictive behaviors (2019) · cites this paper as Gleich et al., 2015
The Discussion reports complementary relationships between prefrontal and striatal glutamate and ventral striatal dopamine synthesis capacity, consistent with coordinated neurochemical activity. But it describes regulation as a potential mechanism, and the Limitations state that the findings are correlational and cannot establish causality. The claim's assertion that these systems *act* in a cross-regulatory fashion is therefore stronger than the paper's finding. (LLM, conf=0.85)
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“and prefrontal areas depend largely upon glutamate and gamma-aminobutyric acid (GABA) (Naaijen, Lythgoe, Amiri, Buitelaar, & Glennon, 2015), and the neurochemical systems involved in fronto-striatal loops act in concerted and cross-regulatory fashions (Gleich et al., 2015).”
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- Authors
- Gleich, T., Deserno, L., Lorenz, R. C., Boehme, R., Pankow, A., Buchert, R., Kuhn, S., Heinz, A., Schlagenhauf, F., & Gallinat, J.
- Affiliations
- Stiftung Charité (DE)
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- Humboldt-Universität zu Berlin (DE)
- Charité – Universitätsmedizin Berlin (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-07-01
- Volume
- 35
- Issue
- 26
- Pages
- 9615-9621
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6605144
- OpenAlex
- W1621815751
- Cited by
- 62
- References
- 75
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 4 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 1
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SCHL 1969/1-1, 01GQ0914, GRK1123, DFG GA707/6-1, GA707/6-1, DFG SCHL1969/1-1, DFG SCHL 1969/2-1)
- Bundesministerium für Bildung und Forschung (01GQ0914)
- Max-Planck-Gesellschaft
- Studienstiftung des Deutschen Volkes
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- ventral striatum, dopamine synthesis capacity, dopamine-glutamate interaction, lateral prefrontal cortex, 1H NMR, schizophrenia
- MeSH terms
- Adult, Corpus Striatum, Dopamine, Female, Humans, Image Processing, Computer-Assisted, Male, Neural Pathways, Magnetic Resonance Spectroscopy, Statistics as Topic, Prefrontal Cortex, Presynaptic Terminals, Glutamic Acid, Fluorodeoxyglucose F18, Positron-Emission Tomography, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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