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Springer Nature [academic journals on nature.com], Neuropsychopharmacology, 5(40), p. 1259-1268, 2014

DOI: 10.1038/npp.2014.312

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The Neurometabolic Fingerprint of Excessive Alcohol Drinking

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.