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. 2018 Oct 24:9:468.
doi: 10.3389/fpsyt.2018.00468. eCollection 2018.

Chronic Alcohol Treatment-Induced GABA-Aα5 Histone H3K4 Trimethylation Upregulation Leads to Increased GABA-Aα5 Expression and Susceptibility to Alcohol Addiction in the Offspring of Wistar Rats

Kuan Zeng  1   2 , Aimin Xie  1   2 , Xiaojie Zhang  3 , Baoliang Zhong  1   2 , Xuebing Liu  1   2 , Wei Hao  3
Affiliations

Chronic Alcohol Treatment-Induced GABA-Aα5 Histone H3K4 Trimethylation Upregulation Leads to Increased GABA-Aα5 Expression and Susceptibility to Alcohol Addiction in the Offspring of Wistar Rats

Kuan Zeng et al. Front Psychiatry. .

Abstract

Gamma-aminobutyric acid (GABA)-Aα5 is considered to be associated with alcohol-induced memory deficits. However, whether it participates in the formation of alcohol addiction or in the regulation of its susceptibility is unknown. Here, we used a chronic alcohol treatment model to obtain alcohol-addicted Wistar rats. Long-term alcoholism increased the expression of prefrontal cortex GABA-Aα5 by inducing its histone H3K4 trimethylation, and these changes could be hereditary and lead to increased vulnerability to alcohol addiction in offspring. This study indicates the risk of long-term alcoholism in future generations, emphasizes the importance of GABA-Aα5 in the formation of alcohol addiction and the regulation of its susceptibility, and provides new evidence regarding the mechanisms underlying alcohol addiction.

Keywords: GABA-Aα5; addiction; alcohol; histone H3K4 trimethylation; offspring.

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Figures

Figure 1
Figure 1
The timeline schematic of rats treatment.
Figure 2
Figure 2
Chronic alcohol treatment increased the conditioned place preference in rats. Rats were divided into four groups. Rats injected with saline or ethanol were denoted as Saline or Ethanol, and each group was divided into male and female by gender. CPP baseline value and CPP test value were recorded. The data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. Saline, two-way ANOVA.
Figure 3
Figure 3
Chronic alcohol treatment increased GABA-Aα5 mRNA levels in the PFC. The relative level of GABA-Aα5 mRNA in the PFC was detected by RT-PCR. The data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. Saline, two-way ANOVA.
Figure 4
Figure 4
Chronic alcohol treatment increased GABA-Aα5 histone H3K9 acetylation and H3K4 trimethylation in the PFC. ChIP-PCR was used to detect the relative level of GABA-Aα5 histone H3K9 acetylation and H3K4 trimethylation. (A) The relative level of GABA-Aα5 histone H3K9 acetylation in the PFC. (B) The relative level of GABA-Aα5 histone H3K4 trimethylation in the PFC. The data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. Saline, two-way ANOVA.
Figure 5
Figure 5
PFC GABA-Aα5 histone H3K4 trimethylation increased in offspring with an alcohol genetic background. ChIP-PCR was used to detect the relative level of GABA-Aα5 histone H3K9 acetylation and H3K4 trimethylation in the PFC of offspring. (A) The relative level of GABA-Aα5 histone H3K9 acetylation in the PFC of offspring. (B) The relative level of GABA-Aα5 histone H3K4 trimethylation in the PFC of offspring. The data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. MSFS, two-way ANOVA.
Figure 6
Figure 6
PFC GABA-Aα5 mRNA levels increased in offspring with an alcohol genetic background. The relative level of GABA-Aα5 mRNA in the PFC of offspring was detected by RT-PCR. The data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. FSMS, two-way ANOVA.
Figure 7
Figure 7
CPP test value increased in offspring with an alcohol genetic background. The offspring were treated with chronic alcohol during the training period and alcohol-related CPP was measured. CPP baseline value and CPP test value were recorded. The data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. CPP baseline value, #p < 0.05 vs. MSFS, two-way ANOVA.
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