Gene mutation can cause excessive alcohol drinking

26 November 2013

Wine in glasses

 

Researchers have discovered a gene that regulates alcohol consumption and, when faulty, can cause excessive drinking in mice.

The study found that normal mice drink little or no alcohol when offered a free choice between a bottle of water and a bottle of diluted alcohol.

However, mice with a mutation in the gene Gabrb1 overwhelmingly preferred drinking alcohol over water, choosing to consume almost 85 per cent of their daily fluid as drinks containing alcohol.

The research was done by a consortium of scientists from five UK universities - Imperial College London, Newcastle University, University of Sussex, UCL and University of Dundee - and the MRC Mammalian Genetics Unit at Harwell.

Working at the MRC Mammalian Genetics Unit, a team led by Professor Howard Thomas from Imperial College London introduced subtle mutations into the genetic code at random throughout the genome and tested mice for alcohol preference.

This led the researchers to identify the gene Gabrb1, which changes alcohol preference so strongly that mice carrying either of two mutations in this gene preferred drinking a 10 per cent alcohol solution - about the strength of wine - over water.

The group showed that mice carrying this mutation were willing to work to obtain the alcoholic drink by pushing a lever and, unlike normal mice, continued to do so even over long periods. They would voluntarily consume enough alcohol in an hour to become intoxicated and have difficulty in coordinating their movements.

Gabrb1 codes for a component of the GABAA receptor, which responds to GABA, a chemical that carries messages between brain cells.

The researchers found that the gene mutation caused the receptor to activate spontaneously, even in the absence of GABA.

These changes were particularly strong in a region of the brain that controls pleasurable emotions and reward, the nucleus accumbens.

Professor Thomas  said: "We know from previous human studies that the GABA system is involved in controlling 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."

Dr Quentin Anstee of Newcastle University said: "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.

"We are continuing our work to establish whether the gene has a similar influence in humans, though we know that in people, alcoholism is much more complicated as environmental factors come into play. But there is the real potential for this to guide development of better treatments for alcoholism in the future."

The paper,  Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition, is published in Nature Communications.

 

  • A consortium of scientists from UK universities and the Medical Research Council (MRC)'s Mammalian Genetics Unit has discovered a gene - Gabrb1 - that regulates alcohol consumption in mice. Mice with a mutation in the gene drank excessively, consuming 85 per cent of their daily fluid intake as drinks containing alcohol. 
  • The research suggests that there may be a genetic component to alcoholism in some individuals. It's hoped that the work may help guide the development of better treatments for alcoholism in the future. 
  • The study was funded by the MRC, Wellcome Trust and ERAB, the European Foundation for Alcohol Research.