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  Impaired Glutamate Homeostasis in the Nucleus Accumbens in Human Cocaine Addiction

Engeli, E., Zoelch, N., Hock, A., Nordt, C., Hulka, L., Kirschner, M., et al. (2020). Impaired Glutamate Homeostasis in the Nucleus Accumbens in Human Cocaine Addiction. Molecular Psychiatry, Epub ahead. doi:10.1038/s41380-020-0828-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-A157-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-A158-1
Genre: Journal Article

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 Creators:
Engeli, EJE, Author
Zoelch, N, Author
Hock, A, Author
Nordt, C, Author
Hulka, LM, Author
Kirschner, M, Author
Scheidegger, M, Author
Esposito, F, Author
Baumgartner, MR, Author
Henning, A1, 2, Author              
Seifritz, E, Author
Quednow, BB, Author
Herdener, M, Author              
Affiliations:
1Research Group MR Spectroscopy and Ultra-High Field Methodology, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528692              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Cocaine addiction is characterized by overwhelming craving for the substance, which drives its escalating use despite adverse consequences. Animal models suggest a disrupted glutamate homeostasis in the nucleus accumbens to underlie addiction-like behavior. After chronic administration of cocaine, rodents show decreased levels of accumbal glutamate, whereas drug-seeking reinstatement is associated with enhanced glutamatergic transmission. However, due to technical obstacles, the role of disturbed glutamate homeostasis for cocaine addiction in humans remains only partially understood, and accordingly, no approved pharmacotherapy exists. Here, we applied a tailored proton magnetic resonance spectroscopy protocol that allows glutamate quantification within the human nucleus accumbens. We found significantly reduced basal glutamate concentrations in the nucleus accumbens in cocaine-addicted (N = 26) compared with healthy individuals (N = 30), and increased glutamate levels during cue-induced craving in cocaine-addicted individuals compared with baseline. These glutamatergic alterations, however, could not be significantly modulated by a short-term challenge of N-acetylcysteine (2400 mg/day on 2 days). Taken together, our findings reveal a disturbed accumbal glutamate homeostasis as a key neurometabolic feature of cocaine addiction also in humans. Therefore, we suggest the glutamatergic system as a promising target for the development of novel pharmacotherapies, and in addition, as a potential biomarker for a personalized medicine approach in addiction.

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 Dates: 2020-06
 Publication Status: Published online
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.1038/s41380-020-0828-z
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Title: Molecular Psychiatry
Source Genre: Journal
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Publ. Info: Houndmills, Hampshire, UK : Stockton Press
Pages: - Volume / Issue: Epub ahead Sequence Number: - Start / End Page: - Identifier: ISSN: 1359-4184
CoNE: https://pure.mpg.de/cone/journals/resource/954925619131