Alcohol-use disorders are diagnosed medical conditions that affect a significant portion of the population in the United States. Symptoms of an alcohol-use disorder includes craving, loss of control, physical dependence, and tolerance. A study out of the United Kingdom’s MRC Mammalian Genetics Unit (MGU) has revealed a gene in mice that controls alcohol consumption, and can lead to alcohol abuse if the gene is mutated.
"Alcohol addiction places a huge burden on the individual, their family, and wider society,” Professor Hugh Perry, chair of the MRC's Neurosciences and Mental Health Board, said in a statement. “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. 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."
According to the Centers for Disease Control and Prevention, 51.5 percent of Americans over the age of 18 admit to being a regular drinker. Alcohol-related deaths, not including accidents and homicides, contribute to 25,692 deaths each year. Around 18 million people in the U.S. are classified as having either alcohol dependence, also known as alcoholism, or alcohol abuse.
Researchers from five different universities in the U.K. isolated a gene in mice known as Gabrb1, and gave each mouse the option to drink either water or diluted alcohol. Outside of the experiment, mice showed little to no interest in alcohol, and were more likely to pick water when given a free choice. However, when the Gabrb1 gene was mutated, the mouse was more likely to drink excessively. In fact, alcoholic drinks made up around 85 percent of daily fluid intake after the gene mutation.
"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, said in the statement. "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."
Not only were mice used in the experiment more likely to pick alcohol over water but they were even willing to work to obtain alcohol by pushing a lever for an extended period of time. Excessive drinking was traced back to single base-pair point mutations in the gene Gabrb1. Gabrb1 is recognized as an important function in the beta 1 subunit and therefore essential to the brain’s GABAA receptor. These mutations increased electrical activity in the area of the brain that controls pleasure.
"We know from previous human studies that the GABA system is involved in controlling alcohol intake,” Professor Howard Thomas, from Imperial College London, said in the statement. “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."
Source: Anstee Q, Perry H, Knapp S, et al. Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. Nature Communications. 2013.