Browsing by Author "Biddle, Matthew"
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Item The role of estrogen receptor manipulation on persistent fear memory induced by traumatic stress exposure(University of Delaware, 2022) Biddle, MatthewPost traumatic stress disorder (PTSD) is a debilitating psychiatric disorder which stems from fear memory persistence after exposure to a traumatic experience. PTSD is associated with a high socioeconomic cost, as well as a higher prevalence rate in women than in men, though the reason behind this sex difference remains unknown. A possible explanation may be cyclic changes in vascular estrogen release, which may be a contributing factor to the higher prevalence of PTSD, though the role of estrogen receptors in modulating traumatic stress effects has been insufficiently explored. By using a well-validated PTSD model (single prolonged stress – SPS) in female rats, we first studied the effects of antagonizing nuclear estrogen receptors (Experiment 1), finding that SPS induced persistent fear memory (measured using freezing) and that this response was not affected by antagonism of nuclear estrogen receptors. Following this, we examined the effects of agonizing G-protein coupled estrogen receptors (GPERs, Experiment 2), finding that SPS had no effect on persistent fear memory, and that activation of GPERs prior to SPS had no effect on persistent fear memory. Finally, we studied the effects of activating estrogen receptors utilizing 17β-estradiol, and found that SPS increased persistent fear memory (measured using darting), and that this enhancement in persistent fear memory was attenuated by activation of estrogen receptors prior to SPS. Overall, the results of the study suggest that SPS effects on persistent fear memory can be observed in female rats (by measuring multiple behaviors) and that increasing estrogen levels prior to SPS attenuates persistent fear memory induced by SPS in female rats.Item The role of estrogen receptor manipulation during traumatic stress on changes in emotional memory induced by traumatic stress(Psychopharmacology, 2023-03-06) Biddle, Matthew; Knox, DayanRationale: 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.