PMID- 25814047 OWN - NLM STAT- MEDLINE DCOM- 20160824 LR - 20181113 IS - 1095-953X (Electronic) IS - 0969-9961 (Print) IS - 0969-9961 (Linking) VI - 82 DP - 2015 Oct TI - Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. PG - 607-619 LID - S0969-9961(15)00091-1 [pii] LID - 10.1016/j.nbd.2015.03.019 [doi] AB - Binge drinking is common during adolescence and can lead to the development of psychiatric disorders, including alcoholism in adulthood. Here, the role and persistent effects of histone modifications during adolescent intermittent ethanol (AIE) exposure in the development of anxiety and alcoholism in adulthood were investigated. Rats received intermittent ethanol exposure during post-natal days 28-41, and anxiety-like behaviors were measured after 1 and 24 h of the last AIE. The effects of AIE on anxiety-like and alcohol-drinking behaviors in adulthood were measured with or without treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). Amygdaloid brain regions were collected to measure HDAC activity, global and gene-specific histone H3 acetylation, expression of brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated (Arc) protein and dendritic spine density (DSD). Adolescent rats displayed anxiety-like behaviors after 24 h, but not 1 h, of last AIE with a concomitant increase in nuclear and cytosolic amygdaloid HDAC activity and HDAC2 and HDAC4 levels leading to deficits in histone (H3-K9) acetylation in the central (CeA) and medial (MeA), but not in basolateral nucleus of amygdala (BLA). Interestingly, some of AIE-induced epigenetic changes such as, increased nuclear HDAC activity, HDAC2 expression, and decreased global histone acetylation persisted in adulthood. In addition, AIE decreased BDNF exons I and IV and Arc promoter specific histone H3 acetylation that was associated with decreased BDNF, Arc expression and DSD in the CeA and MeA during adulthood. AIE also induced anxiety-like behaviors and enhanced ethanol intake in adulthood, which was attenuated by TSA treatment via normalization of deficits in histone H3 acetylation of BDNF and Arc genes. These novel results indicate that AIE induces long-lasting effects on histone modifications and deficits in synaptic events in the amygdala, which are associated with anxiety-like and alcohol drinking behaviors in adulthood. CI - Published by Elsevier Inc. FAU - Pandey, Subhash C AU - Pandey SC AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA. Electronic address: scpandey@uic.edu. FAU - Sakharkar, Amul J AU - Sakharkar AJ AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA. FAU - Tang, Lei AU - Tang L AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA. FAU - Zhang, Huaibo AU - Zhang H AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA. LA - eng GR - R29 AA010005/AA/NIAAA NIH HHS/United States GR - AA-013341/AA/NIAAA NIH HHS/United States GR - I01 BX000143/BX/BLRD VA/United States GR - AA-010005/AA/NIAAA NIH HHS/United States GR - U01 AA019971/AA/NIAAA NIH HHS/United States GR - AA-019971/AA/NIAAA NIH HHS/United States GR - R01 AA010005/AA/NIAAA NIH HHS/United States GR - R01 AA013341/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150324 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Central Nervous System Depressants) RN - 0 (Cytoskeletal Proteins) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Histones) RN - 0 (Hydroxamic Acids) RN - 0 (Nerve Tissue Proteins) RN - 0 (activity regulated cytoskeletal-associated protein) RN - 3K9958V90M (Ethanol) RN - 3X2S926L3Z (trichostatin A) RN - EC 3.5.1.98 (Hdac2 protein, rat) RN - EC 3.5.1.98 (Histone Deacetylase 2) SB - IM MH - Acetylation/drug effects MH - Alcoholism/*metabolism/pathology/prevention & control MH - Animals MH - Anxiety Disorders/*metabolism/pathology/prevention & control MH - Binge Drinking/*metabolism/pathology MH - Brain/*drug effects/*growth & development/metabolism/pathology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Central Nervous System Depressants/toxicity MH - Cytoskeletal Proteins/metabolism MH - Disease Models, Animal MH - Ethanol/toxicity MH - Gene Expression/drug effects MH - Histone Deacetylase 2/metabolism MH - Histone Deacetylase Inhibitors/pharmacology MH - Histones/*drug effects/metabolism MH - Hydroxamic Acids/pharmacology MH - Male MH - Nerve Tissue Proteins/metabolism MH - Rats, Sprague-Dawley MH - Underage Drinking PMC - PMC4581895 MID - NIHMS674956 OTO - NOTNLM OT - Adolescent binge drinking OT - Alcohol intake OT - Amygdala OT - Anxiety OT - Epigenetic OT - HDAC2 OT - Histone acetylation EDAT- 2015/03/31 06:00 MHDA- 2016/08/25 06:00 PMCR- 2016/10/01 CRDT- 2015/03/28 06:00 PHST- 2014/12/03 00:00 [received] PHST- 2015/03/15 00:00 [revised] PHST- 2015/03/16 00:00 [accepted] PHST- 2015/03/28 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2016/08/25 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - S0969-9961(15)00091-1 [pii] AID - 10.1016/j.nbd.2015.03.019 [doi] PST - ppublish SO - Neurobiol Dis. 2015 Oct;82:607-619. doi: 10.1016/j.nbd.2015.03.019. Epub 2015 Mar 24.