Scientists from the National University of Singapore (NUS Medicine) Yong Lu Lin School of Medicine have found that the CHRNA3 gene regulates the body's sensitivity to alcohol. The results were published in the Journal of Neuroscience (JNeurosci).
To determine how genetics influence alcohol use, the researchers used a two-choice approach. participants could voluntarily choose to drink alcohol or not during the experiment. This allowed them to assess the degree of desire and aversion to alcohol and to analyze the activity of genes responsible for neurotransmitter receptors in the brain. Researchers have found that people with active CHRNA3 experience stronger cravings for alcohol.
Normal individuals experience a short-term urge to drink quickly, which becomes aversion as the dose increases. However, in laboratory models with a mutation in the CHRNA3 gene, this transition occurred more slowly; animals consumed alcohol for longer periods and tolerated higher concentrations.
The mutation altered the activity of glutamate and GABA receptors, which are responsible for balancing excitatory and inhibitory signals in the brain. This reduced the typical sedative effects of low doses of alcohol and altered behavioral responses.
“Our study provides direct experimental evidence that ChrNA3 regulates alcohol sensitivity. Variants that alter its function may increase the risk of addiction in humans. "Understanding these risk factors will enable the development of more effective prevention and treatment methods," said study leader Ajay S. Mathuru.
Scientists now plan to expand their research. They are going to analyze the interactions of individual and combined mutations in the CHRNA5-CHRNA3-CHRNB4 gene cluster and assess their relationship to drug addiction.
