Mice with a mutation to the gene Gabrb1 overwhelmingly preferred drinking alcohol over water, UK researchers have found.
The study showed that normal mice show no interest in alcohol and drink little or no alcohol when offered a free choice between a bottle of water and a bottle of diluted alcohol.
The mice with the mutation chose to consume almost 85 per cent of their daily fluid as drinks containing alcohol – about the strength of wine.
"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," Dr Quentin Anstee, Consultant Hepatologist at Newcastle University, joint lead author said.
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 single base-pair point mutations in this gene preferred drinking alcohol over water.
The group showed that mice carrying this mutation were willing to work to obtain the alcohol-containing drink by pushing a lever and, unlike normal mice, continued to do so even over long periods.
They would voluntarily consume sufficient alcohol in an hour to become intoxicated and even have difficulty in coordinating their movements.
The cause of the excessive drinking was tracked down to single base-pair point mutations in the gene Gabrb1, which codes for the beta 1 subunit, an important component of the GABAA receptor in the brain.
This receptor responds to the brain's most important inhibitory chemical messenger (GABA) to regulate brain activity.
The researchers found that the gene mutation caused the receptor to activate spontaneously even when the usual GABA trigger was not present.
These changes were particularly strong in the region of the brain that controls pleasurable emotions and reward, the nucleus accumbens.
"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," Anstee said.
The study was published in the journal Nature Communications.


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