title: Effects of histone deacetylase inhibitor sodium butyrate on heroin seeking behavior in the nucleus accumbens in rats.
abstract: Histone acetylation and other modifications of the chromatin are important regulators of gene expression and may contribute to drug-induced behaviors and neuroplasticity. Inhibition of histone deacetylases (HDAC) activity results in the change of some drug-induced behaviors，however, relatively little is known about the effects of HDAC inhibitors on heroin-seeking behavior. In the present study, male rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, followed by 14 daily 2h extinction session in the operant chamber. After training, the heroin priming (250μg/kg) was introduced for the reinstatement of heroin-seeking behavior. Pretreatment with sodium butyrate (NaB) (200 or 400mg/kg, i.p.), an inhibitor of HDAC, failed to affect heroin self-administration. Additionally，systemic administration of NaB (400mg/kg, i.p.)increased significantly the reinstatement of heroin-seeking induced by heroin priming when NaB administered 12h, but not 6h before the reinstatement test. The same effect was observed after the intracerebroventricular injection of NaB (5μL, 100μg/μL). Moreover, the levels of histone H3 acetylation at lysine 18（H3K18）and H4 acetylation at lysine 5 or lysine 8（H4K5 or H4K8）in the accumbens nucleus core and shell were remarkably increased during the reinstatement and were further strengthened after intracerebroventricular injection of NaB. These results demonstrated that activation of histone acetylation may be involved in the heroin-seeking behavior, and identifying these epigenetic changes will be critical in proposing a novel pharmacological strategy for treating heroin addiction.
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China.
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China.
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Xu
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China.
authors.forename: Hua-Qiang
authors.initials: HQ
authors.lastname: Zhu
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China.
authors.forename: Miao-Jun
authors.initials: MJ
authors.lastname: Lai
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Zhang
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China. Electronic address: whzhou@vip.163.com.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhou
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, PR China. Electronic address: lihufen@163.com.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Liu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D003932:Heroin / Q000008:administration & dosage; D006556:Heroin Dependence / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009294:Narcotics / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009294:Narcotics; D020148:Butyric Acid; D003932:Heroin; D006655:Histone Deacetylases
keywords: Addiction; Epigenetic; Heroin; Histone acetylation; Self-administration