title: Translational magnetic resonance spectroscopy reveals excessive central glutamate levels during alcohol withdrawal in humans and rats.
abstract: 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.
authors: Department of Addiction Medicine, Central Institute for Mental Health, Mannheim, Germany.
authors: Derik
authors: D
authors: Hermann
authors: Wolfgang
authors: W
authors: Weber-Fahr
authors: Alexander
authors: A
authors: Sartorius
authors: Mareen
authors: M
authors: Hoerst
authors: Ulrich
authors: U
authors: Frischknecht
authors: Nuran
authors: N
authors: Tunc-Skarka
authors: Stephanie
authors: S
authors: Perreau-Lenz
authors: Anita C
authors: AC
authors: Hansson
authors: Bertram
authors: B
authors: Krumm
authors: Falk
authors: F
authors: Kiefer
authors: Rainer
authors: R
authors: Spanagel
authors: Karl
authors: K
authors: Mann
authors: Gabriele
authors: G
authors: Ende
authors: Wolfgang H
authors: WH
authors: Sommer
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D016022:Case-Control Studies; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D000431:Ethanol; D018698:Glutamic Acid