A robust study led by researchers at Linköping University has uncovered a molecular mechanism in the brain that is believed central to the development of alcohol addiction. The research potentially explains why some people are more prone to alcoholism than others and may even lead to a new drug therapy than could treat alcohol dependance.
"We have to understand that a core feature of addiction is that you know it is going to harm you, potentially even kill you, and nevertheless something has gone wrong with the motivational control and you keep doing it", says Markus Heilig, co-lead on the new study.
So, the researchers set out to better understand what is going on in the brain that leads to a choice being made despite the negative consequences. An experiment was set up with rats where the animals where given a free choice between sweetened water and alcohol. The alcohol, triggered by pressing a lever, was more difficult for the animals to access than the sweetened water.
After a period of time it was observed that only about 15 percent of the rats continued to work harder to get the alcohol over the sweetened water. Interestingly, the researchers note that this percentage is similar to the amount of humans suffering from alcohol addiction. When the scientists added a small electric shock to the lever supplying the alcohol they observed that the rats still continued to reach out for the substance.
So what was different between the rats who sought out the alcohol despite the negative consequences and the rats that didn't?
After measuring the expression of hundreds of specific genes in the alcoholic rats the researchers homed in on one particular gene. Situated in the amygdala, a region of the brain previously implicated in alcohol dependence, this gene is known to regulate a protein called GAT-3. In the rats prone to alcoholism, expression of this gene was significantly lower than normal, and subsequently, levels of GAT-3 were notably lower than normal. Going even further the researchers then selectively knocked out GAT-3 expression in rats that had previously chosen sweetened water over alcohol.
"Decreasing the expression of the transporter had a striking effect on the behavior of these rats. Animals that had preferred the sweet taste over alcohol reversed their preference and started choosing alcohol", says Eric Augier, lead investigator in the project.
Finally, the study set out to find some correlation in human subjects by examining GAT-3 levels in amygdala tissue samples from deceased individuals with diagnosed alcohol addiction. Excitingly, the results verified that these subjects suffering from alcoholism indeed did display lower GAT-3 levels than normal human subjects.
"This is one of those relatively rare times where we find an interesting change in our animal models and we find the same change in the brains of human alcoholics," says Dayne Mayfield, co-author of the new study. "It's a very good indication that our animal model is correct. And if our animal model is correct, we can screen therapeutics with it and have increased confidence in the findings."
One thing that isn't clear at this stage is what leads to a person developing lower levels of GAT-3. It could be simply genetic, or it could be a more complex array of environmental factors that stimulate a deficiency in this neurological mechanism. Either way, this is an impressive piece of research that adds weight to the argument that alcohol addiction is not a psychological condition, but a more comprehensive neurological disease.
The study was published in the journal Science.
Source: Linköping University
