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Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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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2015 (English)In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 12, no 7, 7154-7171 p.Article in journal (Refereed) Published
Abstract [en]

Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the alpha 2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the alpha 2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to 2A-adrenoceptor agonists.

Place, publisher, year, edition, pages
2015. Vol. 12, no 7, 7154-7171 p.
Keyword [en]
alpha 2A-adrenoceptor, alcohol, brain, gene expression, rat, maternal separation, stress
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:uu:diva-261997DOI: 10.3390/ijerph120707154ISI: 000359342300004PubMedID: 26121187OAI: oai:DiVA.org:uu-261997DiVA: diva2:851845
Funder
Swedish Research Council, K2012-61X-22090-01-3The Swedish Brain Foundation, PS2013-0052
Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2017-12-04Bibliographically approved

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Comasco, ErikaTodkar, AniruddhaGranholm, LinneaNilsson, Kent W.Nylander, Ingrid

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Comasco, ErikaTodkar, AniruddhaGranholm, LinneaNilsson, Kent W.Nylander, Ingrid
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Neuro-psycho-pharmacologyDepartment of Pharmaceutical BiosciencesCentre for Clinical Research, County of Västmanland
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