title: Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal.
abstract: OBJECTIVE
  Neurophysiological and pathological effects of ethanol may be mediated, to an important extent, via the glutamatergic system. Animal studies indicate the acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor. Persistent attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in the compensatory up-regulation of NMDA receptors. Whether glutamatergic neurotransmission and oxidative stress are enhanced during ethanol withdrawal in humans is unknown.
  
  
  METHODS
  CSF was obtained from 18 matched comparison subjects and from 18 patients with alcohol dependence 1 week and 1 month after cessation of ethanol ingestion. CSF samples were analyzed for excitatory neurotransmitters, gamma-aminobutyric acid (GABA), and markers for oxidative stress.
  
  
  RESULTS
  The alcohol-dependent patients' CSF levels of aspartate, glycine, and N-acetylaspartylglutamate were all higher than those of the comparison subjects, and their concentration of GABA was lower. In addition, there were significant correlations between excitatory neurotransmitters and oxidative stress markers, which suggest that the two mechanisms may play an interactive role in neurotoxicity mediated by ethanol withdrawal.
  
  
  CONCLUSIONS
  The data suggest that augmentation of excitatory neurotransmission may lead to enhanced oxidative stress, which, in concert with reduced inhibitory neurotransmission, may contribute to the symptoms of ethanol withdrawal and associated neurotoxicity in humans. Whether these abnormalities represent a trait- or state-dependent marker of ethanol dependence remains to be resolved.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, USA. TSAIG@Helix.MGH.Harvard.edu
authors.forename: G E
authors.initials: GE
authors.lastname: Tsai
authors.forename: P
authors.initials: P
authors.lastname: Ragan
authors.forename: R
authors.initials: R
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: V M
authors.initials: VM
authors.lastname: Linnoila
authors.forename: J T
authors.initials: JT
authors.lastname: Coyle
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D001224:Aspartic Acid / Q000378:metabolism / Q000502:physiology; D004151:Dipeptides / Q000378:metabolism / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism / Q000502:physiology; D005260:Female; D005971:Glutamates / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000134:cerebrospinal fluid / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology
chemical_list: D004151:Dipeptides; D018846:Excitatory Amino Acids; D005971:Glutamates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C027172:isospaglumic acid; D001224:Aspartic Acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D013482:Superoxide Dismutase