Glutamatergic and neurometabolic alterations in chronic cocaine users measured with 1H-magnetic resonance spectroscopy

Lea M. Hulka, Milan Scheidegger, Matthias Vonmoos, Katrin H. Preller, Markus R. Baumgartner, Marcus Herdener, Erich Seifritz, Anke Henning, Boris B. Quednow

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 1H-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. Glutamate and glutamine levels in the pgACC and the rDLPFC measured with 1H-MRS did not differ between cocaine users and controls but higher weekly cocaine use and cocaine hair concentrations were associated with lower glutamine/creatine in the pgACC. Cocaine users exhibited higher glucose/creatine than controls in the pgACC and higher choline/creatine in the pgACC and rDLPFC. Thus, cocaine use is associated with altered glucose metabolism and membrane turnover and appears to decrease glutamine levels indicating changes in glutamate cycling.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalAddiction Biology
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • Anterior cingulate cortex
  • choline
  • cocaine addiction
  • glutamate
  • glutamine
  • magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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