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The Paradoxical Relationship Between Stress and Stress Hormones

After a hiatus, I have returned to writing as I realized how important accurate science communication can be in the hands of the public. Recently, I was invited to write a blog for the European Behavioural Pharmacology Society. While a bit dense for our typical audience, I thought I would cross-post it here anyways as a nice welcome back post. Below I summarize a paper from Vanderhoof et al. that looks at the relationship between environmental stress and corticosterone (CORT), which is a stress hormone inside the body (1). Interestingly, this paper found that when CORT and environmental stress are given together, they have opposite effects to either CORT or environmental stress alone. See below for more details.


This paper presents acute glucocorticoid administration as a potential therapeutic avenue that may mitigate some of the long-term impairments that occur following acute stress exposure during adolescence. Specifically, this pre-clinical study in male mice found that acute corticosterone (CORT) administered immediately after adolescent stress exposure reduced social avoidance, anhedonia, and drug-seeking behaviour in the long-term, i.e. once the mice reached adulthood. This is important because the authors also found that adolescent stress on its own can increase drug-seeking behaviour, anhedonia, and social avoidance later in life, and from the literature we know that these behaviours are associated with an increased susceptibility towards developing a psychiatric disorder. Furthermore, this research is a promising step on the path towards understanding the mechanisms of resilience in the brain and how we can use that knowledge to innovate preventative treatments that could help reverse some of the adverse effects of adolescent stress exposure.


Interestingly, CORT administered in the absence of adolescent stress was associated with an increase in drug-seeking behaviour and social avoidance. As such, CORT and adolescent stress had similar effects when administered in isolation from each other. Paradoxically, only when administered together do we see this reversal effect of these adverse behaviours. This emphasizes the complicated and temporally sensitive role of glucocorticoids in managing the stress response, and therefore CORT administration should be carefully considered when exploring its capacity to promote resilience.


This paper also investigated the ability of CORT administration to attenuate adverse behaviours following adult stress exposure. As it turns out, CORT administered in adult mice immediately after exposure to stress was successful at attenuating fear and drug-seeking behaviour. This was only the case when administered together; in isolation both CORT and adult stress increased drug-seeking behaviour. Fear behaviour was amplified by stress exposure but was not affected by CORT. Furthermore, when stress exposure is closely followed by acute glucocorticoid administration, it has the potential to promote resilience in both adolescent and adult populations. In summary, this paper provides compelling pre-clinical evidence for the use of glucocorticoids to reverse long-term adverse behavioural effects associated with stress exposure, and future investigations into the translational potential of these findings in both humans and females are highly anticipated.


Written by Jess


  1. Vanderhoof, S. O., Vincent, C. J., Beaver, J. N., Latsko, M. S., Aguilar-Alvarez, R., & Jasnow, A. M. (2024). Corticosterone after early adolescent stress prevents social avoidance, aversive behavior, and morphine-conditioned place preference in adulthood. Psychopharmacology, 1-15.

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