Abstract
Animal models for stress-related mood disorders aim to mirror the diverse spectrum of stress responses observed in humans, which ultimately determine an individual's vulnerability or capacity to cope effectively with the stressor. The acute social defeat stress (ASDS) protocol allows a rapid phenotypic classification of mice subjected to social stress to interrogate the early neural patterns beyond divergent stress outcomes. Although ASDS alone doesn't cause chronic depression-like behaviors, it "primes" the mouse to be highly susceptible to a subsequent, subthreshold stress (StSDS). Here, we tested whether pharmacological manipulation shortly before ASDS can counter this susceptibility priming. Specifically, we examined the β-adrenergic receptor antagonist propranolol and the glucocorticoid corticosterone. Male mice received acute intraperitoneal injections of propranolol, corticosterone, or saline prior to ASDS, followed one week later by StSDS and social interaction testing. Propranolol partially prevented the emergence of social avoidance following subsequent StSDS, without modifying the behavioral outcome of ASDS. In contrast, corticosterone administered at different doses, failed to prevent susceptibility priming to later StSDS, disrupting also the typical acute ASDS behavioral profiling at low and medium doses. The results suggest that blocking β-adrenergic signaling during an acute stressor can reduce future stress susceptibility, while underscoring the complex and dose-dependent effects of glucocorticoids on stress responsivity.