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

Neural Regeneration Research 2012年第13期7卷 1021-1028页

作者： Yahui Xu Xuebing Liu Xiaojie Zhang Guanbai Zhang Ruiling Zhang Tieqiao Liu Wei Hao Mental Health Institute Second Xiangya Hospital Central South University Changsha 410011 Hunan Province China Townsend Family Laboratories Graduate Program in Neuroscience University of British Columbia 2255 Wesbrook Mall Vancouver B. C V6T 1Z3 Canada Second Affiliated Hospital of Xinxiang Medical University Xinxiang 453003 Henan Province China

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.

关键词： ethanol seeking chronic ethanol exposure htr3a histone deacetylase histone acetylation sodiumbutyrate neural regeneration

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