Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation

Ann N. Hoffman, Alejandro Parga, Pooja R. Paode, Lucas R. Watterson, Ella M Nikulina, Ronald P Hammer, Cheryl D. Conrad

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6. h/d/21. d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40. mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalNeurobiology of Learning and Memory
Volume120
DOIs
StatePublished - Apr 1 2015

Fingerprint

Amygdala
Fear
Messenger RNA
Post-Traumatic Stress Disorders
Long-Term Memory
Sirolimus
Phenotype
Brain
Hypertrophy
Freezing
Rodentia
Learning

Keywords

  • Amygdala
  • Chronic stress
  • Fear conditioning
  • Hippocampus
  • MTOR
  • PTSD
  • Rapamycin
  • Reconsolidation

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Experimental and Cognitive Psychology

Cite this

Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation. / Hoffman, Ann N.; Parga, Alejandro; Paode, Pooja R.; Watterson, Lucas R.; Nikulina, Ella M; Hammer, Ronald P; Conrad, Cheryl D.

In: Neurobiology of Learning and Memory, Vol. 120, 01.04.2015, p. 61-68.

Research output: Contribution to journalArticle

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