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Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats
Uppsala Univ, Dept Neurosci, S-75124 Uppsala, Sweden..ORCID iD: 0000-0002-2174-2068
Uppsala Univ, Dept Neurosci, S-75124 Uppsala, Sweden..
Uppsala Univ, Dept Pharmaceut Biosci, Neuropharmacol Addict & Behav Grp, S-75124 Uppsala, Sweden..
Vasteras Hosp, Clin Res Ctr, S-72189 Vasteras, Sweden..ORCID iD: 0000-0002-8853-2508
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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, p. 7154-7171Article 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
MDPI AG , 2015. Vol. 12, no 7, p. 7154-7171
Keywords [en]
alpha 2A-adrenoceptor, alcohol, brain, gene expression, rat, maternal separation, stress
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:mdh:diva-52011DOI: 10.3390/ijerph120707154ISI: 000359342300004PubMedID: 26121187Scopus ID: 2-s2.0-84933567414OAI: oai:DiVA.org:mdh-52011DiVA, id: diva2:1484410
Available from: 2020-10-28 Created: 2020-10-28 Last updated: 2021-01-20Bibliographically approved

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Nilsson, Kent W.

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