期刊
BRAIN RESEARCH
卷 1646, 期 -, 页码 418-425出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2016.06.019
关键词
Morphine; Behavioral sensitization; Ventrolateral orbital cortex; Histone acetylation; Erk; Bdnf
资金
- National Natural Science Foundation of China [81172903, 81471820, 81430048, 81371230]
- China Postdoctoral Science Foundation [2014M560760]
- Natural Science Basic Research Plan in Shaanxi Province of China [2015JM3122]
- Fundamental Research Funds for the Central Universities (Projects of International Cooperation and Exchanges) [2015gjhz19]
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 ERR (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. (C) 2016 Elsevier B.V. All rights reserved.
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