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Alcohol Clin Exp Res. 2017 Feb;41(2):323-333. doi: 10.1111/acer.13308. Epub 2017 Jan 18.

Negative Association Between MR-Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats.

Author information

1
Department of Addictive Behavior and Addiction Medicine , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
2
Department of Neuroimaging , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
3
Research Group for Translational Imaging , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
4
Department of Biostatistics , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
5
Institute of Psychopharmacology , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Abstract

BACKGROUND:

Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats.

METHODS:

Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence.

RESULTS:

In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model.

CONCLUSIONS:

Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.

KEYWORDS:

Alcohol Withdrawal; Glutamate; Gray Matter; Hippocampus; Magnetic Resonance Spectroscopy

PMID:
28098946
DOI:
10.1111/acer.13308
[Indexed for MEDLINE]

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