Corticosterone after acute stress prevents the delayed effects on the amygdala

Abstract

Even a single 2-hour episode of immobilization stress is known to trigger anxiety-like behavior and increase spine-density in the basolateral amygdala (BLA) of rats 10 days later. This delayed build-up of morphological and behavioral effects offers a stress-free time window of intervention after acute stress, which we used to test a protective role for glucocorticoids against stress. We observed that post-stress corticosterone, given 1 day after acute stress in drinking water, reversed enhanced anxiety-like behavior 10 days later. Quantification of spine-density on Golgi-stained BLA principal neurons showed that the same intervention also prevented the increase in spine numbers in the amygdala, at the same delayed time-point. Further, stress elevated serum corticosterone levels in rats that received vehicle in the drinking water. However, when stress was followed 24 h later by corticosterone in the drinking water, the surge in corticosterone was prevented. Together, these observations suggest that corticosterone, delivered through drinking water even 24 h after acute stress, is capable of reversing the delayed enhancing effects on BLA synaptic connectivity and anxiety-like behavior. Strikingly, although the immobilization-induced surge in corticosterone by itself has delayed detrimental effects on amygdalar structure and function, there exists a window of opportunity even after stress to mitigate its impact with a second surge of exogenously administered corticosterone. This provides a framework in the amygdala for analyzing how the initial physiological and endocrine processes triggered by traumatic stress eventually give rise to debilitating emotional symptoms, as well as the protective effects of glucocorticoids against their development.

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Fig. 1: Corticosterone in drinking water after stress prevents increase in anxiety-like behavior 10 days later.
Fig. 2: Corticosterone in drinking water after stress prevents impairment in social interaction with a juvenile rat 10 days later.
Fig. 3: Post-stress corticosterone prevents the delayed increase in spine-density in the basolateral amygdala (BLA).
Fig. 4: Post-stress corticosterone treatment leads to a reduction in stress-induced increase in serum corticosterone levels.

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Acknowledgements

PC and SC would like to express their unending gratitude to Prof. Bruce McEwen for his generous advice and continued guidance during this project, from the early days of its conceptualization to its completion.

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PC, BM and SC contributed to the experimental design. PC and SD performed the experiments and analyzed the data. PC, BM and SC interpreted the results. PC and SC wrote the manuscript.

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Correspondence to Sumantra Chattarji.

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Chakraborty, P., Datta, S., McEwen, B.S. et al. Corticosterone after acute stress prevents the delayed effects on the amygdala. Neuropsychopharmacol. (2020). https://doi.org/10.1038/s41386-020-0758-0

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