One Mutation Turns Normal Mice Into Alcoholics

Alcoholism is a complicated condition caused by many factors, but at least one of these factors is your genes.

Researchers have just found a new suspect: the Gabrb1 gene, which seems to play a role in regulating alcohol intake.

Researchers have previously identified 39 genes associated with alcoholism in humans, so we already knew that it has a genetic component. The new study, published in the journal Nature Communications on Nov. 26., zooms in on one specific mutation on one gene that causes alcoholic-like behaviour.

“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,” study researcher Quentin Anstee, of Newcastle University, said in a press release. “But there is the real potential for this to guide development of better treatments for alcoholism in the future.”

The researchers think this mutation messes up the reward pathway in humans, which may lead to alcohol dependence.

In the study the researchers found that normal mice preferred regular water when given the choice between a bottle of water and a bottle of diluted alcohol (about the strength of wine). However, mice with a mutation on the Gabrb1 gene overwhelmingly preferred the alcohol. They consumed almost 85 per cent of their daily fluids from the alcohol bottle.

Mouse alcohol consumptionAnstee, et. al, Nat. Comm., 2013Chart A shows that mutant mice preferred alcohol to water, B shows they drank more alcohol per day.

And the mutated mice worked hard for their booze. They would repeatedly push a lever to get access to the alcohol, while the regular mice wouldn’t. They voluntarily consumed enough alcohol in an hour to become intoxicated and have trouble coordinating their movement.

The mutation seems to affect the GABA system in the brain — the system responsible for keeping us calm and part of the reward pathway. The interruption to this system causes extra stimulation of the nucleus accumbens — a region in the middle of the brain that’s previously been associated with alcohol reward. In humans, alcohol consumption triggers the release of dopamine in the nucleus accumbens and makes us want to drink more. This can lead to the development of an addiction.

“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 researchers acknowledge that there are many other factors that contribute to alcohol addiction in humans, but this research is an important step forward in understanding how the addiction develops.

The Gabrb1 gene is located on chromosome four in humans, but more research is needed to determine if a mutation on the gene could contribute to alcohol dependence in humans.

“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,” Hugh Perry, from the Medical Research Council, said in the press release.

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