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  Chronic cocaine use is associated with glutamatergic and other neurometabolic alterations: a proton magnetic resonance spectroscopy study

Hulka, L., Scheidegger, M., Vonmoos, M., Preller, K., Baumgartner, M., Herdener, M., et al. (2015). Chronic cocaine use is associated with glutamatergic and other neurometabolic alterations: a proton magnetic resonance spectroscopy study. Suchttherapie, 16(S 01): P_07.

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Hulka, LM, Author
Scheidegger, M, Author
Vonmoos, M, Author
Preller, KH, Author
Baumgartner, MR, Author
Herdener, M, Author              
Seifritz, E, Author
Henning, A1, 2, Author              
Quednow, BB, Author
1Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              
2Research Group MR Spectroscopy and Ultra-High Field Methodology, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528692              


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 Abstract: Introduction: Cocaine addiction is a chronically relapsing disorder that is associated with harmful consequences. Effective pharmacotherapies are sparse and the frequently occurring relapses remain a major challenge in the treatment of cocaine use disorder. Preclinical studies suggest that altered glutamatergic signaling from the prefrontal cortex to the nucleus accumbens core is crucial for the maintenance of cocaine-seeking. More specifically, rats showed significantly reduced extracellular glutamate levels in the nucleus accumbens core after extinction from repeated cocaine self-administration and increased synaptic glutamate release in response to cocaine-conditioned cues. It has been posited that altered synaptic plasticity presumably mediates the maladaptive, uncontrolled drug-use behavior observed in addicted cocaine users. Purpose of the study: The translational validity of the above outlined animal models, and thus, if comparable glutamatergic alterations also occur in human cocaine users is currently largely unknown. Gaining a better understanding of how potential glutamatergic alterations in human cocaine users may be associated with the long-lasting vulnerability to relapse might contribute to the development of novel medications to treat cocaine use disorder. Method: We investigated potential differences of glutamate, glutamine and further metabolite concentration ratios in the pregenual anterior cingulate cortex (pgACC) and the right dorsolateral prefrontal cortex (rDLPFC) of 18 male cocaine users and 18 male controls using the PRior knOwledge FITting 2.0 (PROFIT 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. Results: Cocaine users and controls did not differ with regard to glutamate/- and glutamine/creatine concentration ratios (p > 0.3) but cocaine users exhibited higher glucose/total creatine ratios in the pgACC (F (1.20) = 4.89, p < 0.05) and higher choline/creatine ratios in the pgACC (F (1.29) = 2.85, p = 0.05) and rDLPFC (F (1.25) = 4.49, p < 0.05) than controls. Moreover, correlation analyses showed that higher weekly cocaine use (r = –0.59, p < 0.05) and higher cocaine hair concentrations (r = –0.57, p < 0.05) were associated with lower glutamine/creatine ratios in the pgACC. Conclusion: The present results suggest that cocaine use over the past 6 months is associated with decreased cortical glutamine levels, possibly representing changes in glutamate cycling. In addition, altered cortical glucose metabolism and membrane turnover could reflect undetected hemorrhagic or ischemic micro strokes and hence demyelination and gliosis. For future investigations it would be informative to investigate glutamatergic alterations in the nucleus accumbens and to obtain information about compartmental glutamate-glutamine changes by means of 13C-magnetic resonance spectroscopy.


 Dates: 2015-09
 Publication Status: Published in print
 Pages: -
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 Rev. Type: -
 Identifiers: DOI: 10.1055/s-0035-1557701
 Degree: -


Title: Deutscher Suchtkongress 2015
Place of Event: Hamburg, Germany
Start-/End Date: 2015-09-16 - 2015-09-18

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Title: Suchttherapie
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 16 (S 01) Sequence Number: P_07 Start / End Page: - Identifier: ISSN: 1439-9903
CoNE: https://pure.mpg.de/cone/journals/resource/111006902711086