Citation

Meinhardt MW, Sévin DC, Klee ML, Dieter S, Sauer U, Sommer WH. Neuropsychopharmacology 2014; 40(5): 1259-1268.

Affiliation

Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Copyright

(Copyright © 2014, Nature Publishing Group)

DOI

10.1038/npp.2014.312

PMID

25418809

Abstract

'Omics'-techniques are widely used to identify novel mechanism underlying brain function and pathology. Here we applied a novel metabolomics approach to further ascertain the role of fronto-striatal brain regions for the expression of addiction-like behaviors in rat models of alcoholism. Rats were made dependent via chronic intermittent alcohol vapor exposure. Following a three-week abstinence period rats had continuous access to alcohol in a two-bottle, free-choice paradigm for seven weeks. Non-targeted flow injection time-of-flight mass spectroscopy was used to assess global metabolic profiles of two cortical (prelimbic, infralimbic) and two striatal (accumbens core and shell) brain regions. Alcohol consumption produces pronounced global effects on neurometabolomic profiles leading to a clear separation of metabolic phenotypes between treatment groups, particularly. When further comparing regional tissue levels of various metabolites, most notably dopamine and Met-enkephalin, allow the extrapolation of alcohol consumption history. Finally, a high-drinking metabolic fingerprint was identified indicating a distinct alteration of central energy metabolism in the accumbens shell of excessively drinking rats that could indicate a so far unrecognized pathophysiological mechanism in alcohol addiction. In conclusion, global metabolic profiling from distinct brain regions by mass spectrometry identifies profiles reflective of an animal's drinking history and provides a versatile tool to further investigate pathophysiological mechanisms in alcohol dependence.Neuropsychopharmacology accepted article preview online, 24 November 2014. doi:10.1038/npp.2014.312.

Language: en