The University of Chicago is the recipient of a $5 million, five-year grant from the National Institute on Drug Abuse (NIDA) to investigate how social isolation during adolescence may affect vulnerability to drug addiction later in life. The project, co-led by neuroscientists Stephanie Groman, PhD and Zhuzhu Zhang, PhD, brings together experts in behavioral neuroscience and genomics to explore both the behavioral and biological consequences of adolescent social experiences.
Scientists have observed that when animals and people are isolated for long periods of time, their subsequent drug use tends to increase. Following COVID-19-related periods of social distancing, for example, experts raised the alarm about spikes in alcohol sales, alcohol-related deaths, and reports of heavy drinking behavior.
In some cases, these behavioral changes can be fleeting, but researchers have noticed that when isolation occurs during adolescence, the changes are more persistent.
“These observations suggest that isolation during a specific period can subsequently alter the brain in a way that has a long-lasting effect,” Groman said. “Adolescence is a period in which the brain undergoes profound neurodevelopmental change, and it seems like there’s a developmental window in which decision-making functions can be irrecoverably reduced. We want to know what’s happening in that window.”
The study will use rat models to closely mimic adolescent development in humans. By isolating rats for different two-week blocks during their adolescent stage, the researchers can pinpoint when social interaction is most essential for healthy development of the brain areas related to decision-making.
After pinpointing the window of peak vulnerability, the researchers plan to explore the behavioral mechanisms responsible for the elevations in drug use observed in adult rats who were isolated during adolescence.
“We see over and over again that decision-making factors predict subsequent drug-taking, but we have no idea why some animals choose to consume more cocaine than others,” Groman said. “It’s the same question raised by the fact that, say, I like caffeine more than other people: Is it because I value it, or is it because I can't really control my behaviors? Getting into the behaviors that regulate this in a way that really hasn't been done is exciting for me.”
Finally, the collaboration will use advanced single-cell genomics techniques to examine how social isolation disrupts gene activity in brain circuits linked to decision-making and reward. This molecular work may reveal targets for future interventions that can restore or protect healthy brain function.
“Combining my lab’s expertise in behavioral neuroscience and circuitry mapping with the Zhang lab’s expertise in genomics allows for this incredibly powerful set of studies to examine every dimension, from very high-level behavior all the way down to single nucleus genomics,” Groman said. “This grant is an example of how true, integrative team science enables big projects that will hopefully produce big findings.”
Groman also emphasized that the two labs will not just be doing complementary work in parallel; genomics researchers and trainees from Zhang’s lab will come to Groman’s lab and learn to conduct behavioral experiments, and members of the Groman lab will cross-train on molecular and genomics work.
While the experiments use animal models, the researchers hope the findings will inform approaches to supporting adolescent mental health and preventing addiction in humans. Although it’s not feasible to directly measure the same processes in human teenagers, the research may suggest strategies like environmental enrichment or new treatments to help at-risk adolescents.
“This research is going to allow us to generate new hypotheses about addiction susceptibility and a new understanding of how adolescent social isolation and adolescent social exposure modulate those things,” Groman said.
Research reported in this publication was supported by the National Institutes of Health/National Institute on Drug Abuse U01DA064003-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
