title: Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.
abstract: Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial.
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Keller
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States.
authors.forename: William B
authors.initials: WB
authors.lastname: Schreiber
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States.
authors.forename: Briana R
authors.initials: BR
authors.lastname: Stanfield
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States. Electronic address: dknox@psych.udel.edu.
authors.forename: Dayan
authors.initials: D
authors.lastname: Knox
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000096:biosynthesis*; D003463:Cues; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011619:Psychotropic Drugs; D003345:Corticosterone; D008797:Metyrapone
keywords: Anxiety; Fear; Fear memory resistance; Hippocampus; PTSD; Single prolonged stress
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