Translational neurobiochemistry and morphometry of the hippocampus during alcohol withdrawal in humans and rats using MR spectroscopy

Einleitung: Based on previous findings of elevated glutamate concentrations in the anterior cingulate cortex during alcohol withdrawal (AWS), we investigated the neurobiology of the hippocampus. The hippocampus plays an important role in learning and plasticity and is hypothesised to be a key region in the development and maintenance of addiction. Both alcohol consumption and glutamatergic neuroexcitotoxicity is thought to damage brain tissue. Therefore we additionally related brain metabolism to morphometry in a translational approach.

Methode: Alcohol dependent patients (N = 40) underwent a single voxel MR spectroscopy at 3 Tesla during unmedicated AWS and after 14 days of abstinence. A comparison group of (N = 33) was scanned once. Metabolite concentrations and regional hippocampal volumes were quantified. Male wistar rats were treated with an ethanol vapour exposure paradigm (N = 8, AWS) and were compared to 7 control rats. MR spectroscopy at 9.4 Tesla was performed on animals at baseline, three times after 50 cycles of ethanol vapour exposure (AWS) and after 3 weeks of abstinence.

Diskussion/Ergebnisse: We found no alterations in hippocampal Glx (sum of glutamate and glutamine) but significantly reduced levels of N-acetylaspartate (NAA) during AWS in rats and humans. In humans, NAA levels recovered during 14 days abstinence, but only in those patients that did not need Benzodiazepine-treatment for AWS. After 14 days of abstinence Glx was negatively correlated with hippocampal volume. In the rat-model we found a significant increase in the glutamate/glutamine ratio during AWS.

Schlussfolgerung: We could not replicate higher glutamate levels during AWS in the hippocampus of the patients, but animal data of increased Glu/Gln ratio are in concordance with the glutamate hypothesis of alcoholism. Reductions in NAA levels were observed in the hippocampus during AWS but vanished shortly after ethanol cessation. More severe AWS impaired hippocampal recovery. The negative correlation of Glx to hippocampal volume was interpreted as a neuroexcitotoxic effect.