Journal
BIOLOGICAL PSYCHIATRY
Volume 71, Issue 11, Pages 1015-1021Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2011.07.034
Keywords
Alcoholism; chronic intermittent alcohol vapor exposure; glutamate-glutamine cycle; human; neuroimaging; rat model
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB636, 01GS08152, TRANSALC 01EW1112]
- Bundesministerium fur Bildung und Forschung
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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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