中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2012, Vol. 7 ›› Issue (13): 1021-1028.

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

Histone acetylation of the htr3a gene in the prefrontal cortex of Wistar rats regulates ethanol-seeking behavior

  

  • 收稿日期:2012-01-16 修回日期:2012-03-24 出版日期:2012-05-05 发布日期:2012-05-05

Histone acetylation of the htr3a gene in the prefrontal cortex of Wistar rats regulates ethanol-seeking behavior

Yahui Xu1, Xuebing Liu1, Xiaojie Zhang2, Guanbai Zhang1, Ruiling Zhang3, Tieqiao Liu1, Wei Hao1, 3   

  1. 1  Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
    2  Townsend Family Laboratories, Graduate Program in Neuroscience University of British, Columbia 2255 Wesbrook Mall, Vancouver, B.C.
    V6T 1Z3, Canada
    3  Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province, China
  • Received:2012-01-16 Revised:2012-03-24 Online:2012-05-05 Published:2012-05-05
  • Contact: Wei Hao, M.D., Professor, Chief physician, Doctoral supervisor, Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province,China; Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003,Henan Province, China weihao57@gmail.com
  • About author:Yahui Xu , M.D., Menta Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province,China

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Abstract:

Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.

Key words: Ethanol seeking, chronic ethanol exposure, htr3a, histone deacetylase, histone acetylation, sodium butyrate, neural regeneration