Mutant genes may trigger alcoholism, study shows

Researchers from the UK have found something that can actually drive mice to drink—and no, it isn’t stress induced by narrowly dodging mousetraps on a daily basis.

 

A joint research project conducted on mice by students from five UK universities—Imperial College London, Newcastle University, UCL, University of Dundee, and University of Sussex—highlighted the effects of a gene called Gabrb1 on regulating alcohol consumption. The study revealed that a mutation in the gene caused mice to drink enough alcohol in 1 hour to render them intoxicated and unable to move properly.

 

The project was funded by the Medical Research Council (MRC), Wellcome Trust, and the European Foundation for Alcohol Research (ERAB). The results of the study were published in the journal Nature Communications.

 

Gabrb1, the alcohol-regulating gene

 

Perhaps unsurprisingly, the researchers found that ordinary mice had no special interest in alcoholic beverages, opting to go for a bottle of normal water over a bottle of diluted alcohol.

 

However, mice with a mutated Gabrb1 gene showed a strong preference for alcoholic beverages, even going as far as to consume about 85% of their daily fluid intake in the form of alcohol.

 

The gene was isolated when researchers from the Imperial College London, supervised by Professor Howard Thomas, worked at the MRC Mammalian Genetics unit to randomly introduce subtle mutations into the mice’s genetic code. Afterwards, they tested the mice for alcohol preference.

 

The researchers were then able to identify the Gabrb1 gene, and found that mice carrying one of two mutations in the gene preferred drinking alcohol (10% ethanol – close to the strength of wine) to ordinary water. This led the researchers to conclude that the mutated gene had a strong influence on the test subjects’ alcohol preference.

 

In fact, the gene’s influence on the mice was strong enough to make them exert physical effort just to get to the alcohol, as the mice had to push a lever to gain access to the drink.

 

Dr Quentin Anstee, a consultant hepatologist at Newcastle University and one of the study’s lead authors, found this remarkable.

“It’s amazing to think that a small change in the code for just one gene can have such profound effects on complex behaviours like alcohol consumption,” he said.

 

The researchers determined that the mutated Gabrb1 caused a receptor in the brain called GABAA to spontaneously activate even in the absence of its usual trigger, the inhibitory chemical messenger GABA.

 

“The mutation of the beta1 containing receptor is altering its structure and creating spontaneous electrical activity in the brain in this pleasure zone, the nucleus accumbens. As the electrical signal from these receptors increases, so does the desire to drink to such an extent that mice will actually work to get the alcohol, for much longer than we would have expected," explained Dr. Anstee.

 

Possible implications for alcoholism in humans

 

According to Professor Thomas, previous studies had already shown that the GABA system has a hand in controlling human alcohol intake.

 

“Our studies in mice show that a particular subunit of GABAA receptor has a significant effect and most importantly the existence of these mice has allowed our collaborative group to investigate the mechanism involved. This is important when we come to try to modify this process first in mice and then in man,” said Thomas.

 

The project was funded by the MRC to discover which genes affected alcohol consumption. The findings of the study are expected to be helpful in treating alcoholism – or even curb-stomping it before it could develop further.

 

“Alcohol addiction places a huge burden on the individual, their family and wider society. There’s still a great deal we don’t understand about how and why consumption progresses into addiction, but the results of this long-running project suggest that, in some individuals, there may be a genetic component,” said Professor Hugh Perry, Chair of the MRC’s Neurosciences and Mental Health Board.

 

“If further research confirms that a similar mechanism is present in humans, it could help us to identify those most at risk of developing an addiction and ensure they receive the most effective treatment.”—TJD, GMA News