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.