From stress to anhedonia: differential gene expression, behavioural and biochemical modulations in resilient versus susceptible mice in an ultrasound model of juvenile depression

Juvenile depression is an increasingly recognized mental health condition, distinct from adult depression. ‘Emotional stress’, i.e., adverse experience of primarily psychological nature, is a risk factor of particular importance for juvenile depression. Like adults, adolescents display variable susceptibility to depression precipitated by stress, the nature of which is poorly understood. We employed the 3-week ultrasound (US) stress in juvenile C57BL/6 mice to compare behavioral and molecular features of susceptible and resilient to depressive-like syndrome subsets of animals. Mice were exposed to alternating frequencies of 20–25 kHz and 25–45 kHz, an established model of ‘emotional stress’. In the sucrose test, mice were categorized as anhedonic (stress-susceptible) or non-anhedonic (stress-resilient), upon their sucrose preference that decreased below control values in some but not all animals. Parameters of emotionality, social and locomotor behaviors, learning, serum corticosterone levels, brain gene expression of pro-inflammatory cytokines, and malondialdehyde (MDA) concentrations were studied. In comparison with controls, susceptible mice exhibited prolonged floating behavior in the swim test, increased anxiety-like and dominant-type social behaviors, elevated corticosterone plasma levels, increased brain expression of cytokines interleukin-1 β (Il-1β) and tumor necrosis factor (Tnf), reduced expression of proteolipid protein 1 (Plp1) and myelin-associated glycoprotein (Mag). These changes were not found in resilient mice. Brain MDA concentrations similarly increased in both groups. Hence, the ultrasound stress model appears to replicate several behavioral features relevant to juvenile depression in mice, suggesting its potential as a tool for investigating various aspects of adolescent depression. Additionally, it introduces the stratification of animals into ‘resilient’ and ‘susceptible’ subgroups, which may contribute to a better understanding of the mechanisms associated with stress resilience during adolescence. © The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2025.