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Ethanol affects limbic and striatal presynaptic glutamatergic and DNA methylation gene expression in outbred rats exposed to early-life stress
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Neuropharmacology, addiction and behaviour)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
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2017 (English)In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 22, no 2, 369-380 p.Article in journal (Refereed) Published
Abstract [en]

Alcohol use disorder is the outcome of both genetic and environmental influences and their interaction via epigenetic mechanisms. The neurotransmitter glutamate is an important regulator of reward circuits and implicated in adaptive changes induced by ethanol intake. The present study aimed at investigating corticolimbic and corticostriatal genetic signatures focusing on the glutamatergic phenotype in relation to early-life stress (ELS) and consequent adult ethanol consumption. A rodent maternal separation model was employed to mimic ELS, and a free-choice paradigm was used to assess ethanol intake in adulthood. Gene expression levels of the Vesicular Glutamate Transporters (Vglut) 1, 2 and 3, as well as two key regulators of DNA methylation, DNA (cytosine-5)-methyltransferase 1 (Dnmt1) and methyl-CpG-binding protein 2 (Mecp2), were analyzed. Brain regions of interest were the ventral tegmental area (VTA), nucleus accumbens (Acb), medial prefrontal cortex (mPFC) and dorsal striatum (dStr), all involved in mediating aspects of ethanol reward. Region-specific Vglut, Dnmt1 and Mecp2 expression patterns were observed. ELS was associated with down-regulated expression of Vglut2 in the VTA and mPFC. Rats exposed to ELS were more sensitive to ethanol-induced changes in Vglut expression in the VTA, Acb, and dStr and in Dnmt1 and Mecp2 expression in the striatal regions. These findings suggest long-term glutamatergic and DNA methylation neuroadaptations as a consequence of ELS, and show an association between voluntary drinking in non-preferring, non-dependent, rodents and different Vglut, Dnmt1 and Mecp2 expression depending on early-life history.

Place, publisher, year, edition, pages
2017. Vol. 22, no 2, 369-380 p.
Keyword [en]
Alcohol, DNA methylation, glutamate, rats, stress, Vgluts
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-276528DOI: 10.1111/adb.12331ISI: 000394988500008PubMedID: 26610727OAI: oai:DiVA.org:uu-276528DiVA: diva2:903296
Funder
Swedish Research Council, K2012-61X-22090-01-3 2013-4657 2014-3804Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-0627Lars Hierta Memorial FoundationThe Swedish Brain Foundation, PS2013-0052
Available from: 2016-02-15 Created: 2016-02-15 Last updated: 2017-04-27Bibliographically approved

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Vrettou, MariaGranholm, LinneaTodkar, AniruddhaNilsson, Kent W.Wallén-Mackenzie, ÅsaNylander, IngridComasco, Erika

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Vrettou, MariaGranholm, LinneaTodkar, AniruddhaNilsson, Kent W.Wallén-Mackenzie, ÅsaNylander, IngridComasco, Erika
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Department of NeuroscienceDepartment of Pharmaceutical BiosciencesCentre for Clinical Research, County of Västmanland
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