Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder

Ann N. Hoffman, Nickolaus G. Lorson, Federico Sanabria, Michael Olive, Cheryl Conrad

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6. h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalNeurobiology of Learning and Memory
Volume112
DOIs
StatePublished - Jul 2014

Keywords

  • BLA
  • CA1
  • CEA
  • Fear conditioning
  • Generalization
  • Non-associative learning
  • PTSD
  • Restraint

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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