From Casual to Compulsive: How Brain Circuitry Affects Alcohol Use

The Context: Alcohol use disorders affect roughly 15 million Americans, but why some people are more susceptible to compulsive drinking than others is not well understood.

The Study: A new study in Science by NYSCF – Robertson Neuroscience Investigator and Salk Institute Professor Dr. Kay Tye identifies a brain circuit that regulates alcohol consumption in mice and that may be predictive of compulsive drinking.

The Importance: This study helps us to understand why some people become compulsive drinkers, and may point to ways to intervene in alcohol use or other impulse-related disorders.

Why is it that some people can drink casually and others become compulsive drinkers? A new study in Science by NYSCF – Robertson Neuroscience Investigator and Salk Institute Professor Kay Tye, PhD, identifies a brain circuit that regulates alcohol consumption in mice and that may be predictive of compulsive 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 behavior starts,” said Dr. Tye in a press release. “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.”

“We initially sought to understand how the brain is altered by binge drinking to drive compulsive alcohol consumption,” remarked Cody Siciliano, PhD, first author and assistant professor in the Department of Pharmacology at Vanderbilt University. “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 study compulsive drinking, the researchers developed a ‘binge-induced compulsion task’ (BICT) for mice, sorting them into three groups: low drinkers, high drinkers, and compulsive drinkers (those who continued to drink even when alcohol consumption was paired with negative consequences such as bitter taste). They then used advanced imaging techniques to map brain activity before, during, and after the mice consumed alcohol.

The scientists kept a close eye on two brain regions related to behavioral control and processing adverse experiences: the medial prefrontal cortex and periaqueductal gray matter. Mice who developed compulsive drinking showed increased activity between these two areas, and this activity was also predictive of future drinking behavior. By controlling the activity of this brain circuit using optogenetics (a technique pioneered by NYSCF–Robertson Investigator Alumnus Dr. Ed Boyden that allows researchers to modify cell behavior using light), the team was able to promote or silence compulsive drinking on demand.

These findings have important implications for understanding alcohol-related diseases and other impulse disorders in humans, as well as how these conditions could be treated or prevented.

“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 Dr. 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.”

Journal Article

A cortical-brainstem circuit predicts and governs compulsive alcohol drinking
Cody A. Siciliano, Habiba Noamany, Chia-Jung Chang, Alex R. Brown, Xinhong Chen, Daniel Leible, Jennifer J. Lee, Joyce Wang, Amanda N. Vernon, Caitlin M. Vander Weele, Eyal Y. Kimchi, Myriam Heiman, Kay M. Tye. Science. 2019. DOI: 10.1126/science.aay1186