title: Glutamatergic and neurometabolic alterations in chronic cocaine users measured with (1) H-magnetic resonance spectroscopy.
abstract: Cocaine addiction is a chronically relapsing disorder that is associated with harmful consequences. Relapses occur frequently and effective pharmacotherapies are currently sparse. Preclinical studies suggest that altered glutamatergic signaling is crucial for the maintenance of cocaine self-administration. However, the translational validity of these models is currently unknown. Therefore, we investigated potential differences of glutamate, glutamine and further metabolite levels in the pregenual anterior cingulate cortex (pgACC) and the right dorsolateral prefrontal cortex (rDLPFC) of chronic cocaine users and controls using the PRior knOwledge FITting 2.0 tool in combination with two-dimensional J-resolved single-voxel (1) H-magnetic resonance spectroscopy at 3T and voxel tissue composition and relaxation correction. Glutamate and glutamine levels did not differ between cocaine users and controls, but higher weekly cocaine use and higher cocaine hair concentrations were associated with lower glutamine/creatine ratios in the pgACC. Interestingly, cocaine users exhibited higher glucose/total creatine ratios than controls in the pgACC and higher choline/creatine ratios in the pgACC and rDLPFC. These results imply that cocaine use is associated with altered cortical glucose metabolism and membrane turnover. Finally, cocaine use over the past 6 months appears to decrease cortical glutamine levels indicating changes in glutamate cycling.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Hulka
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.|Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland.
authors.forename: Milan
authors.initials: M
authors.lastname: Scheidegger
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vonmoos
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.
authors.forename: Katrin H
authors.initials: KH
authors.lastname: Preller
authors.affiliation: Institute of Legal Medicine, University of Zurich, Switzerland.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Baumgartner
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Herdener
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.|Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland.|Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Henning
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland.
authors.forename: Boris B
authors.initials: BB
authors.lastname: Quednow
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000473:pathology; D003401:Creatine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: Anterior cingulate cortex; choline; cocaine addiction; glutamate; glutamine; magnetic resonance spectroscopy