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The role of estrogen receptor manipulation during traumatic stress on changes in emotional memory induced by traumatic stress

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Abstract

Rationale

Traumatic stress leads to persistent fear, which is a core feature of post-traumatic stress disorder (PTSD). Women are more likely than men to develop PTSD after trauma exposure, which suggests women are differentially sensitive to traumatic stress. However, it is unclear how this differential sensitivity manifests. Cyclical changes in vascular estrogen release could be a contributing factor where levels of vascular estrogens (and activation of estrogen receptors) at the time of traumatic stress alter the impact of traumatic stress.

Methods

To examine this, we manipulated estrogen receptors at the time of stress and observed the effect this had on fear and extinction memory (within the single prolonged stress (SPS) paradigm) in female rats. In all experiments, freezing and darting were used to measure fear and extinction memory.

Results

In Experiment 1, SPS enhanced freezing during extinction testing, and this effect was blocked by nuclear estrogen receptor antagonism prior to SPS. In Experiment 2, SPS decreased conditioned freezing during the acquisition and testing of extinction. Administration of 17β-estradiol altered freezing in control and SPS animals during the acquisition of extinction, but this treatment had no effect on freezing during the testing of extinction memory. In all experiments, darting was only observed to footshock onset during fear conditioning.

Conclusion

The results suggest multiple behaviors (or different behavioral paradigms) are needed to characterize the nature of traumatic stress effects on emotional memory in female rats and that nuclear estrogen receptor antagonism prior to SPS blocks SPS effects on emotional memory in female rats.

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The research in this manuscript was supported by an NIH grant 1P20GM103653.

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  1. Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, USA

    Matthew Biddle & Dayan Knox

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  2. Dayan Knox
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M.B. conducted experiments, did PubMed searches on the manuscript, and helped write the manuscript. D.K. designed the experiment, helped edit and write the manuscript, and analyzed the data.

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Correspondence to Dayan Knox.

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Biddle, M., Knox, D. The role of estrogen receptor manipulation during traumatic stress on changes in emotional memory induced by traumatic stress. Psychopharmacology 240, 1049–1061 (2023). https://doi.org/10.1007/s00213-023-06342-6

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