Brain biomarker can predict compulsive drinking

US researchers have discovered a brain circuit that controls alcohol drinking behaviour in mice, and can be used as a biomarker for predicting the development of compulsive drinking later on. Published in the journal Science, their findings could potentially have implications for understanding human binge drinking and addiction in the future.

Although alcohol use is ubiquitous in modern society, only a portion of individuals develop alcohol use disorders or addiction — yet scientists have not understood why some individuals are more prone to develop drinking problems. And while previous research has focused on examining the brain after a drinking disorder develops, the Salk Institute’s Professor Kay Tye and her team sought to discover the brain circuits that are responsible for a predisposition for compulsive drinking to develop in the first place.

“We initially sought to understand how the brain is altered by binge drinking to drive compulsive alcohol consumption,” said Cody Siciliano, assistant professor at Vanderbilt University and first author on the study. “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.”

The researchers created a test called a binge-induced compulsion task (BICT) to examine how susceptibility towards alcohol consumption interacts with experience to produce compulsive drinking in mice. The BICT allowed the researchers to examine alcohol consumption as well as consumption with negative consequences, such as a bitter taste added to the alcohol. Through a series of tests, the scientists observed that the mice could be sorted into three groups: low drinkers, high drinkers and compulsive drinkers. Unlike the first two groups, the compulsive drinkers showed insensitivity to negative consequences.

The researchers then used an imaging technique called microendoscopic single-cell resolution calcium imaging to chart the cells and brain regions of interest prior to drinking, during drinking and after drinking alcohol. Specifically, they looked at neuron activity in two regions involved in behavioural control and responding to adverse events: the medial prefrontal cortex and the periaqueductal grey matter, respectively.

They found that the development of compulsive alcohol drinking was related to neural communication patterns between the two brain regions, and was a biomarker for predicting future compulsive drinking. By using optogenetics to turn the brain circuit on or off, the scientists were able to either increase compulsive alcohol drinking or reduce it.

Nuclei (blue) of the medial prefrontal cortex neurons projecting their axons (green) to the periaqueductal grey area. Image credit: Salk Institute.

“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,” Prof Tye said. Next, the scientists plan to sequence the cortical-brainstem neurons in order to identify targets that could be used for therapeutics.

“We do not know if this brain circuit is specific to alcohol or if the same circuit is involved in multiple different compulsive behaviours such as those related to other substances of abuse or natural rewards, so that is something we need to investigate.”

Top image credit: ©stock.adobe.com/au/Photographee.eu

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