Journal
ADDICTION BIOLOGY
Volume 22, Issue 2, Pages 369-380Publisher
WILEY
DOI: 10.1111/adb.12331
Keywords
Alcohol; DNA methylation; glutamate; rats; stress; Vgluts
Categories
Funding
- Alcohol Research Council of the Swedish Alcohol Retailing Monopoly
- European Foundation for Alcohol Research [EA 11 30]
- Swedish Research Council [K2012-61X-22090-01-3, 2013-4657, 2014-3804]
- Swedish Council for Working Life and Social Research [2011-0627]
- Fredrik and Ingrid Thuring Foundation
- Lars Hierta's Minne Foundation
- Swedish Brain Foundation [PS2013-0052]
- Lundberg's and Karlsson's Foundation
- Uppsala University
- Swedish Brain Foundation
- Hallsten Research Foundation
- Ahlen Foundation
- Alcohol Research Council of the Swedish Alcohol Retailing Monopoly (SRA)
- Swedish Council for Working Life and Social Research (FAS)
- Uppsala and Orebro Regional Research Council
- Fredrik and Ingrid Thurings Foundation
- County Council of Vastmanland
- Konig-Soderstromska Foundation
- Swedish Psychiatric Foundation
- Svenska Spel Research Foundation
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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.
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