Is There a Biomarker for Compulsive Drinking?

In a milestone discovery for addiction research, a team of scientists from the Salk Institute have discovered a brain biomarker that could help predict compulsive drinking. During mice trials, the team isolated a brain circuit linked to excessive alcohol consumption and the potential development of disorders or addiction. Until now, little was known about the physiological markers associated with drinking problems. While stress and trauma are obvious "nurture" factors, the influence of "nature" and genetics has been largely unexplored.

Bridging the gap between brain circuit analysis and compulsive drinking

The findings were published in the journal Science, with the researchers asserting the study could have major implications for understanding more about the mechanics and drivers of alcoholism. While previous studies have focused on examining the brain after an alcohol addiction has already developed, Salk Institute researcher Kay Tye and her team wanted to explore whether brain circuits can influence a predisposition for excessive drinking.

"I hope this will be a landmark study, as we've found (for the first time) a brain circuit that can accurately predict which mice will develop compulsive alcohol drinking weeks before the behaviour starts," says Tye, a professor in the Systems Neurobiology Laboratory. "This research bridges the gap between circuit analysis and alcohol/addiction research, and provides a first glimpse at how representations of compulsive alcohol drinking develop across time in the brain."

Neural activity used to predict alcoholism

Cody Siciliano, first author of the study explains, "We initially sought to understand how the brain is altered by binge drinking to drive compulsive alcohol consumption. In the process, we stumbled across a surprising finding where we were actually able to predict which animals would become compulsive based on neural activity during the very first time they drank."

To test the theory, the team created a binge-induced compulsion task (BICT) test designed to analyse how predisposition for heavy alcohol consumption can facilitate compulsive drinking in mice. As well as observing behaviours towards regular alcohol, the team observed reactions to negative consequences such as the addition of a bitter taste. After analysing drinking habits, the mice were sorted into three groups – low drinkers, heavy drinkers and compulsive drinkers. Unlike low and heavy drinkers, the compulsive mice were not put off by negative consequences.

A proactive approach to preventing addiction

An advanced technique called microendoscopic single-cell resolution calcium imaging was used to map the brain regions and at neuron activity of the mice prior, during and after alcohol consumption. The team found that mice with neural communication between the medial prefrontal cortex and the periaqueductal grey matter regions of the brain were more prone to compulsive alcohol drinking.

"Now, we can look into the brain and find activity patterns that predict if mice will become compulsive drinkers in the future, before the compulsion develops," explains Tye. "We do not know if this brain circuit is specific to alcohol or if the same circuit is involved in multiple different compulsive behaviors such as those related to other substances of abuse or natural rewards, so that is something we need to investigate."

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