PMID- 24103311 OWN - NLM STAT- MEDLINE DCOM- 20140826 LR - 20211021 IS - 1469-5111 (Electronic) IS - 1461-1457 (Print) IS - 1461-1457 (Linking) VI - 17 IP - 2 DP - 2014 Feb TI - Reversal of deficits in dendritic spines, BDNF and Arc expression in the amygdala during alcohol dependence by HDAC inhibitor treatment. PG - 313-22 LID - 10.1017/S1461145713001144 [doi] AB - Development of anxiety-like behaviours during ethanol withdrawal has been correlated with increased histone deacetylase (HDAC) activity and decreased brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc) gene expression in the amygdala. Furthermore, HDAC-mediated histone modifications play a role in synaptic plasticity. In this study we used the HDAC inhibitor trichostatin A (TSA) to determine whether HDAC inhibition could prevent ethanol withdrawal-induced deficits in dendritic spine density (DSD), BDNF or Arc expression in the amygdala of rats. It was found that decreased BDNF and Arc expression in the central (CeA) and medial nucleus of amygdala (MeA), observed during withdrawal after chronic ethanol exposure, were normalized following acute TSA treatment. TSA treatment was also able to attenuate anxiety-like behaviours during ethanol withdrawal and correct the observed decrease in DSD in the CeA and MeA of ethanol-withdrawn rats. Taken together, these findings demonstrate that correcting the deficits in histone acetylation through TSA treatment also amends downstream synaptic plasticity-related deficits such as BDNF and Arc expression, and DSD in the CeA and MeA as well as attenuates anxiety-like behaviours in rats during withdrawal after chronic ethanol exposure. FAU - You, Chang AU - You C AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. FAU - Zhang, Huaibo AU - Zhang H AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. FAU - Sakharkar, Amul J AU - Sakharkar AJ AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. FAU - Teppen, Tara AU - Teppen T AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. FAU - Pandey, Subhash C AU - Pandey SC AD - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. LA - eng GR - R29 AA010005/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 - AA-016690/AA/NIAAA NIH HHS/United States GR - R01 AA010005/AA/NIAAA NIH HHS/United States GR - R01 AA016690/AA/NIAAA NIH HHS/United States GR - R01 AA013341/AA/NIAAA NIH HHS/United States GR - AA-013341/AA/NIAAA NIH HHS/United States GR - AA-010005/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 - 20131009 PL - England TA - Int J Neuropsychopharmacol JT - The international journal of neuropsychopharmacology JID - 9815893 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytoskeletal Proteins) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Nerve Tissue Proteins) RN - 0 (activity regulated cytoskeletal-associated protein) SB - IM MH - Alcoholism/drug therapy/*metabolism/pathology MH - Amygdala/drug effects/*metabolism/pathology MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Cytoskeletal Proteins/*biosynthesis MH - Dendritic Spines/drug effects/*metabolism/pathology MH - Histone Deacetylase Inhibitors/*pharmacology/therapeutic use MH - Male MH - Nerve Tissue Proteins/*biosynthesis MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Substance Withdrawal Syndrome/drug therapy/metabolism/pathology MH - Treatment Outcome PMC - PMC4093912 MID - NIHMS598524 COIS- Conflict of Interest SCP reports that a US patent application on a related topic (serial number 60/848237 filed on September 29(th), 2006) is currently pending. All other authors reported no biomedical financial interests or potential conflicts of interest. EDAT- 2013/10/10 06:00 MHDA- 2014/08/27 06:00 PMCR- 2015/02/01 CRDT- 2013/10/10 06:00 PHST- 2013/10/10 06:00 [entrez] PHST- 2013/10/10 06:00 [pubmed] PHST- 2014/08/27 06:00 [medline] PHST- 2015/02/01 00:00 [pmc-release] AID - S1461145713001144 [pii] AID - 10.1017/S1461145713001144 [doi] PST - ppublish SO - Int J Neuropsychopharmacol. 2014 Feb;17(2):313-22. doi: 10.1017/S1461145713001144. Epub 2013 Oct 9.