How alcohol addiction alters our brain decoded

Scientists have identified how alcohol addiction alters the brain signalling system, which may pave the way to treat the condition in humans.

Researchers, from Linkoping University and University of Gothenburg in Sweden, found that molecular changes in the brain are linked to behaviours that are central to addiction, such as choosing a drug over alternative rewards.

They developed a method where the rats were trained to get alcohol solution by pressing a lever. To understand how addiction causes an individual to choose alcohol over other alternatives, a lever dispensing sweetened water was introduced.

Once the sweetened water came into the picture, a majority of rats chose that over alcohol. Fifteen per cent rats, however, continued to consume alcohol despite the better tasting alternative.

This proportion and behaviour of these rats are strikingly similar to humans with alcohol addiction, researchers said.

"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," said Markus Heilig, a professor at Linkoping University.

To closely scrutinise the mechanism behind the addiction-like traits in the rats, the researchers studied the expression of hundreds of genes in five areas of the brain.

The largest differences were observed in the amygdala, which controlled emotional reactions. In the rats that chose alcohol over sweetened water, the gene which is the blueprint for the protein GAT-3, a transport protein (or 'transporter') that helps maintain moderate levels of the inhibitory signal substance GABA around the nerve cells, was expressed at much lower levels.
The researchers then knocked out GAT-3 in rats that earlier preferred sweetened water over alcohol.

"Decreasing the expression of the transporter had a striking effect on the behaviour of these rats. Animals that had preferred the sweet taste over alcohol reversed their preference and started choosing alcohol," said Eric Augier, from Linkoping University.

To check whether or not these results applied to human beings, the research team analysed GAT-3 levels in brain tissue from deceased humans. In individuals with documented alcohol addiction, GAT-3 levels in the amygdala region were lower than in control individuals, like in the rats.

"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," said Dayne Mayfield, a research scientist from the University of Texas at Austin.

Baclofen, a medication that has long been used to treat increased muscular tension in certain neurological states, is also being studied for treating alcohol dependence.

"One of the things baclofen does is to suppress GABA release. We are currently working with a drug company to try to develop a second-generation molecule as a candidate for alcoholism medication that targets this signalling pathway," Heilig said.