A study from the Salk Institute and Massachusetts Institute of Technology has identified a new brain circuit implicated in compulsive drinking in mice and how to modify it to discourage binge drinking.

Alcohol is the most commonly abused substance with Alcohol Use Disorder (AUD) affecting an estimated 16 million people in the United States. AUD is defined by the NIH as; a chronic relapsing brain disease that is characterised by excessive usage, loss of control over alcohol intake, negative emotions when not drinking, and continued drinking in the face of negative consequences.

To study this condition, the researchers exposed mice to a binge-drinking session over a number of days and recorded their behaviours. Initially mice were given access to unlimited, untreated alcohol before it was spiked by a bitter substance called quinine. The purpose of this was to see whether the mice would continue drinking in spite of the negative consequences – a symptomatic hallmark of AUD.

Observed behaviours of mice were divided into three groups; low, high, and compulsive drinkers. Low drinkers maintained a low alcohol intake throughout, high drinkers consumed markedly more but avoided the spiked quinine alcohol, whilst compulsive drinkers were not fazed by the bitter quinine or by additional punishments such as foot shocking.

The researchers reviewed the mice behaviour to see if there were any predictors of over-alcohol consumption. Previous behaviours showed no significance in influencing later alcohol usage. Prior work suggested that changes in the prefrontal cortex may impact compulsive behaviours. By using a live cell imaging technique, the researchers visualised the neuronal activity in the prefrontal cortex before, during, and after drinking. Significant neuronal changes between the groups were detectable from day 1 of alcohol exposure. Compulsive drinkers had reduced neuronal activity compared to the low drinkers; suggesting that punishment signals were not being transmitted as readily.

After identifying this brain circuit, the researchers investigated ways in which to modify it. One technique performed was optogenetics, which is the stimulation of genetically modified neurons through the use of light. This demonstrated increased neuronal activity in response to alcohol intake; reinforcing the punishment signal in compulsive mice towards alcohol, and thus reducing their intake. This modification provided long-term effects, altering the brain structure of the prefrontal cortex and resulting in a robust long-lasting decrease in overall drinking.

This study identified a predictive biomarker and brain circuit involved in compulsive alcohol use, uncovering the latent differences towards drinking between individuals. Time will tell if this circuit will lead to new therapies, or if it can be applied to other substance abuse disorders.

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