Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Tsai, G. E. Articles by Coyle, J. T. Search for Related Content PubMed Citation Articles by Tsai, G. E. Articles by Coyle, J. T.

Increased Glutamatergic Neurotransmission and Oxidative Stress After Alcohol Withdrawal

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. METHOD: 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, -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.

This article has been cited by other articles:

				M. E. Jung, A. M. Wilson, X. Ju, Y. Wen, D. B. Metzger, and J. W. Simpkins Ethanol Withdrawal Provokes Opening of the Mitochondrial Membrane Permeability Transition Pore in an Estrogen-Preventable Manner J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 692 - 698. [Abstract] [Full Text] [PDF]

				M. E. Jung, J. W. Simpkins, A. M. Wilson, H. F. Downey, and R. T. Mallet Intermittent hypoxia conditioning prevents behavioral deficit and brain oxidative stress in ethanol-withdrawn rats J Appl Physiol, August 1, 2008; 105(2): 510 - 517. [Abstract] [Full Text] [PDF]

				M. E. Jung, A. M. Wilson, and J. W. Simpkins A Nonfeminizing Estrogen Analog Protects against Ethanol Withdrawal Toxicity in Immortalized Hippocampal Cells J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 543 - 550. [Abstract] [Full Text] [PDF]

				J. H. Krystal, J. Staley, G. Mason, I. L. Petrakis, J. Kaufman, R. A. Harris, J. Gelernter, and J. Lappalainen {gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment. Arch Gen Psychiatry, September 1, 2006; 63(9): 957 - 968. [Abstract] [Full Text] [PDF]

				M. E. Jung, M. B. Gatch, and J. W. Simpkins Estrogen Neuroprotection Against the Neurotoxic Effects of Ethanol Withdrawal: Potential Mechanisms Experimental Biology and Medicine, January 1, 2005; 230(1): 8 - 22. [Abstract] [Full Text] [PDF]

				S. BLEICH, K. BAYERLEIN, U. REULBACH, T. HILLEMACHER, D. BONSCH, B. MUGELE, J. KORNHUBER, and W. SPERLING HOMOCYSTEINE LEVELS IN PATIENTS CLASSIFIED ACCORDING TO LESCH'S TYPOLOGY Alcohol Alcohol., November 1, 2004; 39(6): 493 - 498. [Abstract] [Full Text] [PDF]

				A. H. Mack and R. J. Frances Substance-Related Disorders Focus, April 1, 2003; 1(2): 125 - 146. [Abstract] [Full Text] [PDF]

				J. Chick, H. Howlett, M. Y. Morgan, B. Ritson, and f. t. U. I. UNITED KINGDOM MULTICENTRE ACAMPROSATE STUDY (UKMAS): A 6-MONTH PROSPECTIVE STUDY OF ACAMPROSATE VERSUS PLACEBO IN PREVENTING RELAPSE AFTER WITHDRAWAL FROM ALCOHOL Alcohol Alcohol., March 1, 2000; 35(2): 176 - 187. [Abstract] [Full Text] [PDF]

Get information about faster international access.

Privacy Policy

Copyright © 1998 American Psychiatric Association. All rights reserved.

Home | Search | Current Issue | Past Issues | Subscribe | All APPI Journals | Help | Contact Us