title: The neurometabolic fingerprint of excessive alcohol drinking.
abstract: 'Omics' techniques are widely used to identify novel mechanisms underlying brain function and pathology. Here we applied a novel metabolomics approach to further ascertain the role of frontostriatal brain regions for the expression of addiction-like behaviors in rat models of alcoholism. Rats were made alcohol dependent via chronic intermittent alcohol vapor exposure. Following a 3-week abstinence period, rats had continuous access to alcohol in a two-bottle, free-choice paradigm for 7 weeks. Nontargeted flow injection time-of-flight mass spectrometry was used to assess global metabolic profiles of two cortical (prelimbic and 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. Further comparisons of 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.
authors.affiliation: Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Meinhardt
authors.affiliation: 1] Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland [2] PhD Program on Systems Biology, Life Science Zurich, Zurich, Switzerland.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Sévin
authors.affiliation: Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Manuela L
authors.initials: ML
authors.lastname: Klee
authors.affiliation: Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dieter
authors.affiliation: Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.affiliation: 1] Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany [2] Department of Addiction Medicine at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Sommer
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002540:Cerebral Cortex / Q000378:metabolism*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage; D008297:Male; D013058:Mass Spectrometry; D009714:Nucleus Accumbens / Q000378:metabolism*; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D004744:Enkephalin, Methionine; D004298:Dopamine