Episodes of heavy alcohol consumption leading to intoxication are associated with many health and safety problems, including unintentional injuries, sexual assault, domestic violence and alcohol poisoning. Previous studies have shown that brain molecules called GABAA receptors appear to play a role in excessive drinking. In a new study, researchers used an established rat model of binge drinking to investigate how GABAA receptors interact with other brain molecules to influence excessive drinking. The researchers established, for the first time, a direct connection between a molecule known as Toll-like receptor 4 (TLR4) and GABAA receptors. TLR4 is an innate immune system molecule that contributes to the inflammation and brain damage brought on by excessive drinking. Using gene therapy techniques, the researchers targeted TLR4 and GABAA receptors in brains of heavy-drinking rats. They found that silencing the genes for TLR4 and GABAA receptors in certain areas of the brain caused the rats to lose interest in alcohol, an effect that lasted for two weeks after the procedure. The new findings provide exciting new knowledge about the biology of binge drinking in this animal model. It is an important step in understanding brain pathways involved in excessive alcohol consumption and reveals new targets for exploring therapeutic interventions for human drinking.