LA JOLLA (August 25, 2026)—The COVID-19 pandemic tested us in many ways—how we handle crisis, isolation, health, loss, and so much more. Amidst all the conversations about how we cope, one topic came up again and again: alcohol.
"This project really started during the pandemic," says Kay Tye, PhD , Salk professor and Howard Hughes Medical Institute investigator. "Some people said being alone makes them drink less, others said more, so we wondered, is there actually a neural mechanism linking social isolation and alcohol use?"
Tye is co-corresponding author of a new study, published in Nature Neuroscience on August 25, 2026, that asks that very question.
The findings are two-fold: 1) a circuit in the brain is responsible for driving isolation-related drinking, and 2) the circuit has opposing effects in male and female mice. The circuit connects neurons in two brain regions, the basolateral amygdala and medial prefrontal cortex, and its sensitivity may be a powerful biomarker for alcohol use disorder risk. The study also demonstrates the value of studying both male and female biology and suggests optimal treatments likely vary by sex.
What do we know about social isolation and alcohol drinking?
Approximately 7 percent of the global population over the age of 15 battles alcohol use disorder, according to the World Health Organization. While risk factors are sometimes random or genetic, social isolation can be a major contributor to developing the disorder.
Tye is an expert on social isolation and how the brain processes emotion, stress responses, and social information. Two brain regions in particular, the basolateral amygdala and medial prefrontal cortex, are central to these processes—and are already known to contribute to alcohol drinking.
"These brain regions are supposed to be generic cognition regions involved in learning and memory, though they've been consistently observed as involved in social processing and alcohol consumption," says Tye, who holds the Wylie Vale Chair at Salk. "We wanted to know whether social isolation and alcohol consumption had any influence on one another and, if so, find the neuronal circuitry responsible."
Is there a neural circuit controlling social isolation-based alcohol drinking?
The study began with a straightforward assessment of whether male and female mice drank more water or alcohol when housed alone or in large groups. After 11 days of isolation, female mice drank less alcohol, while male mice drank more. The same social trigger had opposing effects in the two sexes.
"I think this really highlights the importance of doing biological research in females because our bodies and brains are not the same—and sometimes, they are the opposite," says Tye.
"The question then becomes why? Why is there this sex-based divergence?" asks co-first author Kelly Kim, a graduate student researcher at the University of Washington.
The scientists then recorded the electrical activity of individual neurons in mouse brains and found that neurons in the basolateral amygdala projected to the medial prefrontal cortex in both female and male mice. The difference was that isolation increased the circuit's excitability in males while decreasing excitability in females.
The team then carried out further mechanistic studies to determine what was driving this escalation in male mice, since their sex was reliably increasing alcohol consumption in response to isolation and would therefore serve as a consistent model for probing the underlying neuronal mechanisms.
Brain imaging revealed that the activity in this circuit could predict when the mice would drink alcohol. And when the pathway was artificially activated, without isolating the mice socially, the same effect was observed—more drinking.
Stimulating the basolateral amygdala pathway made the medial prefrontal cortex pathway more responsive to alcohol. And when that pathway was inhibited in isolated mice, their drinking significantly decreased.
"Social isolation is reconfiguring prefrontal cortex processing in the brain to promote alcohol intake," says Kim. "This is an entirely novel circuit-level explanation for how adverse social experience can bias the brain toward alcohol."
How might these findings inform human alcohol use disorder treatment?
"Abnormal reward response is a hallmark of substance use disorders like alcohol use disorder, and other conditions like depression and anxiety," says co-first and co-corresponding author Reesha Patel, PhD, a former postdoctoral researcher in Tye's lab and current assistant professor at Northwestern University. "The circuit we identified does just that—suppresses responses to natural rewards and amplifies responses to alcohol. By revealing a hard-wired vulnerability to disorder, we hope better therapeutic approaches can begin to take root."
For the 7 percent of adults worldwide living with alcohol use disorder, the researchers envision their findings translating into better risk prediction and treatment strategies.
"I hope these data will be used to inform policies that are not one-size-fits-all for how men and women should be treated with alcohol, drinking, and isolation," says Tye. "Sex is a biological variable that informs our risk factors, yet there are no recommendations or structural systems in place to support men and women experiencing alcohol use disorder differently."
Other authors and funding
Other authors include Makenzie Patarino, Rachelle Pamintuan, Bitna Joo, Anna Pallé, Aniek van Hoek, Jesse White, Christian Cazares, Jeremy Delahanty, Laurel Keyes, Romy Wichmann, and Talmo Pereira of Salk; Felix Taschbach, Christopher Lee, Rogelio Castro, Raymundo Miranda, Caroline Jia, Kanha Batra, and Avraham Libster of Salk and UC San Diego; Hao Li of Salk and Northwestern University; Xianru Yu of Northwestern University; and Marcus Benna of UC San Diego.
The work was supported by the National Institutes of Health (K99/R00 AA029180, R01 MH139476, K99/R00 DA055111, R01 AA031656, K00 MH132569, K12 GM068524, R01 MH115920, R37 MH102441, DP1 AT009925), Whitehall Foundation, Brain and Behavior Research Foundation, Howard Hughes Medical Institute, Kavli Foundation, and Dolby Family Fund.
This press release was written by Isabella Davis.
About the Salk Institute for Biological Studies
The Salk Institute is an independent, nonprofit research institute founded in 1960 by Jonas Salk, developer of the first safe and effective polio vaccine. The Institute's mission is to drive foundational, collaborative, risk-taking research that addresses society's most pressing challenges, including cancer, Alzheimer's, and agricultural vulnerability. This foundational science underpins all translational efforts, generating insights that enable new medicines and innovations worldwide. Learn more at www.salk.edu .
