Abstract
Objective To investigate whether the offspring of chronic ethanol exposured Wistar rats inherited the changes of histone modification. To explore the epigenetic mechanism of the effect of chronic ethanol exposured Wistar rats on the ethanol-seeking behavior of their offspring. Methods Twenty-four male and 24 female adult Wistar rats were randomly injected ethanol and saline for 15 days and experienced withdrawal for 15 days，then coupled into 4 groups. The offspring of the 4 groups were divided into two groups, 48 rats without ethanol exposure and 48 rats with ethanol exposure. Conditioned place preference (CPP) was used to evaluate the ethanol-seeking behavior. Using reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (ChIP) assays, the levels of htr3a mRNA and specific histone modifications in htr3a promoter region of prefrontal cortex (PFC) were determined respectively. Results (1) In the offspring without ethanol exposure, the htr3a mRNA expression level and the H3K9 acetylation in htr3a promoter region were significantly increased in ones with parental ethanol exposured than ones with parental saline exposured (F=31.496, P<0.001; F=10.333, P<0.001). (2) In the offspring with ethanol exposure, the CPP score was significantly higher in ones with parental ethanol exposured than ones with parental saline exposured (F=11.436, P<0.001). The htr3a mRNA expression level and the H3K9 acetylation in htr3a promoter region were significantly higher in offspring of saline exposured rats than ones of ethanol exposured rats (F=26.105, P<0.001; F=3.740, P<0.05). Conclusion Chronic ethanol exposure could induce H3K9 acetylation in htr3a promoter region and be inherited between generations. Parental exposure to ethanol may enhance the ethanol-seeking behavior through mechanisms involving H3K9 acetylation in htr3a promoter region. Key words: Histones; Alcohol-related disorders; htr3a; Wistar rats
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