PMID- 28857504 OWN - NLM STAT- MEDLINE DCOM- 20180830 LR - 20181113 IS - 1601-183X (Electronic) IS - 1601-1848 (Print) IS - 1601-183X (Linking) VI - 17 IP - 2 DP - 2018 Feb TI - Persistent histone modifications at the BDNF and Cdk-5 promoters following extinction of nicotine-seeking in rats. PG - 98-106 LID - 10.1111/gbb.12421 [doi] AB - Drugs of addiction lead to a wide range of epigenetic changes at the promoter regions of genes directly implicated in learning and memory processes. We have previously shown that the histone deactylase inhibitor, sodium butyrate (NaB), accelerates the extinction of nicotine-seeking and provides resistance to relapse. Here, we explore the potential molecular mechanisms underlying this effect. Rats received intravenous nicotine or saline self-administration, followed by 6 days of extinction training, with each extinction session followed immediately by treatment with NaB or vehicle. On the last day of extinction, rats were killed and the medial ventral prefrontal cortex retained for chromatin immunoprecipitation and quantitative polymerase chain reaction (qPCR). A history of nicotine exposure significantly decreased H3K14 acetylation at the brain-derived neurotrophic factor (BDNF) exon IV promoter, and this effect was abolished with NaB treatment. In contrast, nicotine self-administration alone, resulted in a significant decrease in histone methylation at the H3K27me3 and H3K9me2 marks in the promoter regions of BDNF exon IV and cyclin-dependent kinase 5 (Cdk-5). Quantitative PCR-identified changes in several genes associated with NaB treatment that were independent of nicotine exposure; however, an interaction of nicotine history and NaB treatment was detected only in the expression of BDNF IV and BDNF IX. Together these results suggest that nicotine self-administration leads to a number of epigenetic changes at both the BDNF and Cdk-5 promoters, and that these changes may contribute to the enhanced extinction of nicotine-seeking by NaB. CI - (c) 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society. FAU - Castino, M R AU - Castino MR AD - School of Psychology, University of New South Wales, Sydney, Australia. FAU - Baker-Andresen, D AU - Baker-Andresen D AD - Queensland Brain Institute, The University of Queensland, Brisbane, Australia. FAU - Ratnu, V S AU - Ratnu VS AD - Queensland Brain Institute, The University of Queensland, Brisbane, Australia. FAU - Shevchenko, G AU - Shevchenko G AD - Center for Gene Therapy, City of Hope, Duarte, CA, USA. FAU - Morris, K V AU - Morris KV AD - Center for Gene Therapy, City of Hope, Duarte, CA, USA. FAU - Bredy, T W AU - Bredy TW AUID- ORCID: 0000-0003-3280-126X AD - Queensland Brain Institute, The University of Queensland, Brisbane, Australia. FAU - Youngson, N A AU - Youngson NA AD - School of Medical Sciences, University of New South Wales, Sydney, Australia. FAU - Clemens, K J AU - Clemens KJ AUID- ORCID: 0000-0003-2709-218X AD - School of Psychology, University of New South Wales, Sydney, Australia. LA - eng GR - R01 AI111139/AI/NIAID NIH HHS/United States GR - R01 MH113407/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170928 PL - England TA - Genes Brain Behav JT - Genes, brain, and behavior JID - 101129617 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 6M3C89ZY6R (Nicotine) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*drug effects/genetics MH - Conditioning, Operant/drug effects MH - Cyclin-Dependent Kinase 5/*drug effects/genetics MH - Drug-Seeking Behavior MH - Histone Code/drug effects MH - Male MH - Memory/drug effects MH - Nicotine/*pharmacology MH - Promoter Regions, Genetic/*drug effects/genetics MH - Rats, Sprague-Dawley MH - Self Administration PMC - PMC5820208 MID - NIHMS931284 OTO - NOTNLM OT - BDNF OT - cdk-5 OT - epigenetics OT - histone acetylation OT - histone methylation OT - nicotine EDAT- 2017/09/01 06:00 MHDA- 2018/08/31 06:00 PMCR- 2018/02/21 CRDT- 2017/09/01 06:00 PHST- 2017/07/23 00:00 [received] PHST- 2017/08/24 00:00 [revised] PHST- 2017/08/25 00:00 [accepted] PHST- 2017/09/01 06:00 [pubmed] PHST- 2018/08/31 06:00 [medline] PHST- 2017/09/01 06:00 [entrez] PHST- 2018/02/21 00:00 [pmc-release] AID - 10.1111/gbb.12421 [doi] PST - ppublish SO - Genes Brain Behav. 2018 Feb;17(2):98-106. doi: 10.1111/gbb.12421. Epub 2017 Sep 28.