title: Αlpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats.
abstract: 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 α2A-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 α2A-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 α2A-adrenoceptor agonists.
authors.affiliation: Department of Neuroscience, Uppsala University, 75124 Uppsala, Sweden. erika.comasco@neuro.uu.se.
authors.forename: Erika
authors.initials: E
authors.lastname: Comasco
authors.affiliation: Department of Neuroscience, Uppsala University, 75124 Uppsala, Sweden. aniruddha.todkar@neuro.uu.se.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Todkar
authors.affiliation: Neuropharmacology, Addiction & Behaviour Group, Department of Pharmaceutical Biosciences, Uppsala University, 75124 Uppsala, Sweden. linnea.granholm@farmbio.uu.se.
authors.forename: Linnea
authors.initials: L
authors.lastname: Granholm
authors.affiliation: Centre for Clinical Research, Västerås Central Hospital, 72189 Västerås, Sweden. kent.nilsson@ltv.se.
authors.forename: Kent W
authors.initials: KW
authors.lastname: Nilsson
authors.affiliation: Neuropharmacology, Addiction & Behaviour Group, Department of Pharmaceutical Biosciences, Uppsala University, 75124 Uppsala, Sweden. linnea.granholm@farmbio.uu.se.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Nylander
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D007031:Hypothalamus; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*
chemical_list: C547770:Adra2a protein, rat; D005819:Genetic Markers; D018341:Receptors, Adrenergic, alpha-2
keywords: alcohol; brain; gene expression; maternal separation; rat; stress; α2A-adrenoceptor