title: Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function?
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy and NeuroCure Cluster of Excellence in Medical Neuroscience, Charité-University Medicine Berlin, 10117 Berlin, Germany, tobias.gleich@charite.de.
authors.forename: Tobias
authors.identifier: http://orcid.org/0000-0003-1106-0319
authors.initials: T
authors.lastname: Gleich
authors.affiliation: Department of Psychiatry and Psychotherapy and Neurology and Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
authors.forename: Lorenz
authors.identifier: http://orcid.org/0000-0001-7392-5280
authors.initials: L
authors.lastname: Deserno
authors.affiliation: Department of Psychiatry and Psychotherapy and Institute of Psychology, Humboldt University, 12489 Berlin, Germany.
authors.forename: Robert Christian
authors.identifier: http://orcid.org/0000-0003-3286-6792
authors.initials: RC
authors.lastname: Lorenz
authors.affiliation: Department of Psychiatry and Psychotherapy and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Boehme
authors.affiliation: Department of Psychiatry and Psychotherapy and.
authors.forename: Anne
authors.initials: A
authors.lastname: Pankow
authors.affiliation: Department of Nuclear Medicine, Charité-University Medicine Berlin, 12200 Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
authors.affiliation: Department of Psychiatry and Psychotherapy and Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany, and.
authors.forename: Simone
authors.initials: S
authors.lastname: Kühn
authors.affiliation: Department of Psychiatry and Psychotherapy and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Department of Psychiatry and Psychotherapy and Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schlagenhauf
authors.affiliation: Department of Psychiatry and Psychotherapy and Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
mesh_terms: D000328:Adult; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging / Q000378:metabolism*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18; D018698:Glutamic Acid; D004298:Dopamine
keywords: FDOPA PET; MRS; dopamine; glutamate; prefrontal cortex; striatum