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.
Highlights
It is a substance that elicits dependency, alcohol has legitimacy and widespread social acceptance
We found that increased prefrontal cortex (PFC) GABAAα5 expression and its histone H3K4 trimethylation caused by chronic alcohol treatment could be inherited by the offspring, increasing the vulnerability of the offspring to alcohol addiction
The conditioned place preference (CPP) test values were significantly higher than CPP baseline values after chronic alcohol treatment in both the male and female groups (P < 0.05), whereas there was no significant difference between the CPP test values and CPP baseline values in the groups treated with saline, indicating that the two groups of rats formed a clear CPP for alcohol
Summary
It is a substance that elicits dependency, alcohol has legitimacy and widespread social acceptance. In 2015, a study showed that ∼18.3% of adults experienced drunkenness 1 month before the investigation, and 843.2 per 100,000 people were suffering from alcohol addiction [1]. Research on the biological mechanism of mental addiction to addictive substances indicates that the dopamine (DA) system at the edge of the midbrain, which is known as the “reward system,” plays a key role [3]. This theory is consistent with the idea that “there is no addiction without rewards.”. In alcohol addiction, GABA (A) receptors are associated with alcohol tolerance, dependence, and withdrawal [5]
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