Microinjection of histone deacetylase inhibitor into the ventrolateral orbital cortex potentiates morphine induced behavioral sensitization.
Accumulating evidence indicates that epigenetic regulation, such as changes in histone modification in reward-related brain regions, contributes to the memory formation of addiction to opiates and psychostimulants. Our recent results suggested that the ventrolateral orbital cortex (VLO) is involved in the memories of stress and drug addiction. Since addiction and stress memories share some common pathways, the present study was designed to investigate the role of histone deacetylase (HDAC) activity in the VLO during morphine induced-behavioral sensitization. Rats received a single exposure to morphine for establishing the behavioral sensitization model. The effect of HDAC activity in the VLO in morphine induced-behavioral sensitization was examined by microinjection of HDAC inhibitor Trichostatin A (TSA). Furthermore, the protein expression levels of extracellular signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK), histone H3 lysine 9 acetylation (aceH3K9) and brain-derived neurotrophic factor (BDNF) in the VLO in morphine-induced behavioral sensitization were examined. The results showed that the bilateral VLO lesions suppressed the expression phase, but not the developmental phase of morphine-induced behavioral sensitization. Microinjection of TSA into the VLO significantly increased both the development and expression phases. Moreover, the protein levels of p-ERK, aceH3K9 and BDNF except ERK in the VLO were significantly upregulated in morphine-treated rats in the expression phase. These effects were further strengthened by intra-VLO injection of TSA. Our findings suggest that HDAC activity in the VLO could potentiate morphine-induced behavioral sensitization. The upregulated expression of p-ERK, aceH3K9 and BDNF in the VLO might be the underlying mechanism of histone acetylation enhancing the morphine-induced behavioral sensitization.
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Division of Forensic Medicine, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
Lai
L
Wei
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Yuan-Mei
YM
Zhu
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Yu-Xiang
YX
Zhang
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Feng
F
Liang
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Devin M
DM
Barry
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Hong-Yu
HY
Gao
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Tao
T
Li
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China. Electronic address: huofq@mail.xjtu.edu.cn.
Fu-Quan
FQ
Huo
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China. Electronic address: yanchunxia@mail.xjtu.edu.cn.
Chun-Xia
CX
Yan
D000107:Acetylation / Q000187:drug effects; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D019208:Brain-Derived Neurotrophic Factor; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D009020:Morphine; D048049:Extracellular Signal-Regulated MAP Kinases
Bdnf; Behavioral sensitization; Erk; Histone acetylation; Morphine; Ventrolateral orbital cortex