Early life stress in male mice blunts responsiveness in a translationally-relevant reward task

Early-life stress (ELS) leaves signatures upon the brain that persist throughout the lifespan and increase the risk of psychiatric illnesses including mood and anxiety disorders. In humans, myriad forms of ELS-including childhood abuse, bullying, poverty, and trauma-are increasingly prevalent. Understanding the signs of ELS, including those associated with psychiatric illness, will enable improved treatment and prevention. Here, we developed a novel procedure to model human ELS in mice and identify translationally-relevant biomarkers of mood and anxiety disorders. We exposed male mice (C57BL/6 J) to an early-life (juvenile) chronic social defeat stress (jCSDS) and examined social interaction and responsivity to reward during adulthood. As expected, jCSDS-exposed mice showed a socially avoidant phenotype in open-field social interaction tests. However, sucrose preference tests failed to demonstrate ELS-induced reductions in choice for the sweetened solution, suggesting no effect on reward function. To explore whether other tasks might be more sensitive to changes in motivation, we tested the mice in the Probabilistic Reward Task (PRT), a procedure often used in humans to study reward learning deficits associated with depressive illness. In a touchscreen PRT variant that was reverse-translated to maximize alignment with the version used in human subjects, mice exposed to jCSDS displayed significant reductions in the tendency to develop response biases for the more richly-rewarded stimulus, a hallmark sign of anhedonia when observed in humans. Our findings suggest that translationally-relevant procedures that utilize the same endpoints across species may enable the development of improved model systems that more accurately predict outcomes in humans.

Automated summary

Early-life stress has long-lasting impacts on the brain, increasing the risk of psychiatric illnesses. By modeling human early-life stress in mice, researchers have identified biomarkers that are relevant to mood and anxiety disorders, which can potentially improve treatment and prevention strategies.