title: Glucocorticoids are required for extinction of predator stress-induced hyperarousal.
abstract: BACKGROUND
  The role of glucocorticoids in extinction of traumatic memories has not been fully characterized despite its potential as a therapeutic target for acquired posttraumatic stress disorder (PTSD). The predator stress paradigm allows us to determine whether glucocorticoids mediate the extinction of both context-dependent and context-independent fear memories.
  
  
  METHODS
  Male C57BL/6J mice were exposed to a predator (cat) then repeatedly exposed to the predator stress context in the absence of the cat. Context-dependent (associative) fear memory was assessed as suppression of activity during re-exposure to the predator stress context without the cat (extinction trials). Context-independent fear (non-associative) was assessed seven days after extinction trials using measures of hyperarousal and anxiety-like behaviours in environments unlike the predator stress context. To assess the role of glucocorticoids, mice were injected with metyrapone (50mg/kg) 90 min prior to extinction trials in predator stressed mice and context-dependent and context-independent fear memories were assessed. Finally, metyrapone-treated predator stressed mice were injected with corticosterone (5 or 10mg/kg) immediately following extinction trials and context-dependent and context-independent fear memories were assessed.
  
  
  RESULTS
  Repeated re-exposure to the predator stress context without the cat present extinguished context-dependent fear memory, and also reduced hyperarousal, a generalized, chronic PTSD-like symptom. We show that extinction of context-independent predator stress-induced hyperarousal is dependent on endogenous glucocorticoids during the extinction trials. Furthermore, the inhibition of extinction by metyrapone on startle amplitude was reduced by exogenous administration of corticosterone following extinction trials. Overall, these data implicate glucocorticoids in the extinction of hyperarousal, a core symptom of PTSD.
authors: Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave., St. John's, Newfoundland, Canada.
authors: Rachel
authors: R
authors: Clay
authors: Mark
authors: M
authors: Hebert
authors: Greg
authors: G
authors: Gill
authors: Lesley Ann
authors: LA
authors: Stapleton
authors: Allison
authors: A
authors: Pridham
authors: Meaghan
authors: M
authors: Coady
authors: Jillian
authors: J
authors: Bishop
authors: Robert E
authors: RE
authors: Adamec
authors: Jacqueline J
authors: JJ
authors: Blundell
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D003345:Corticosterone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D009812:Odorants; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003345:Corticosterone; D008797:Metyrapone