Translational magnetic resonance spectroscopy reveals excessive central glutamate levels during alcohol withdrawal in humans and rats
Background: In alcoholism, excessive glutamatergic neurotransmission has long been implicated in the acute withdrawal syndrome and as a key signal for dependence-related neuroplasticity. Our understanding of this pathophysiological mechanism originates largely from animal studies, but human data are...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1 June 2012
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| In: |
Biological psychiatry
Year: 2012, Volume: 71, Issue: 11, Pages: 1015-1021 |
| ISSN: | 1873-2402 |
| DOI: | 10.1016/j.biopsych.2011.07.034 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.biopsych.2011.07.034 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0006322311007815 
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| Author Notes: | Derik Hermann, Wolfgang Weber-Fahr, Alexander Sartorius, Mareen Hoerst, Ulrich Frischknecht, Nuran Tunc-Skarka, Stephanie Perreau-Lenz, Anita C. Hansson, Bertram Krumm, Falk Kiefer, Rainer Spanagel, Karl Mann, Gabriele Ende, Wolfgang H. Sommer |
| Summary: | Background: In alcoholism, excessive glutamatergic neurotransmission has long been implicated in the acute withdrawal syndrome and as a key signal for dependence-related neuroplasticity. Our understanding of this pathophysiological mechanism originates largely from animal studies, but human data are needed for translation into successful medication development. Methods: We measured brain glutamate levels during detoxification in alcohol-dependent patients (n = 47) and in healthy control subjects (n = 57) as well as in a rat model of alcoholism by state-of-the-art 1H-magnetic magnetic resonance spectroscopy at 3 and 9.4 T, respectively. Results: We found significantly increased glutamate levels during acute alcohol withdrawal in corresponding prefrontocortical regions of treatment-seeking alcoholic patients and alcohol-dependent rats versus respective control subjects. The augmented spectroscopic glutamate signal is likely related to increased glutamatergic neurotransmission because, enabled by the high field strength of the animal scanner, we detected a profoundly elevated glutamate/glutamine ratio in alcohol-dependent rats during acute withdrawal. All dependence-induced metabolic alterations normalize within a few weeks of abstinence in both humans and rats. Conclusions: Our data provide first-time direct support from humans for the glutamate hypothesis of alcoholism, demonstrate the comparability of human and animal magnetic resonance spectroscopy responses, and identify the glutamate/glutamine ratio as potential biomarker for monitoring disease progression. |
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| Item Description: | Gesehen am 15.05.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1873-2402 |
| DOI: | 10.1016/j.biopsych.2011.07.034 |