Acute nicotine enhances spontaneous recovery of contextual fear and changes c-fos early gene expression in infralimbic cortex, hippocampus, and amygdala

Munir G. Kutlu, Jessica M. Tumolo, Erica Holliday, Brendan Garrett, Thomas J. Gould

Research output: Contribution to journalArticle

13 Scopus citations


Exposure therapy, which focuses on extinguishing fear-triggering cues and contexts, is widely used to treat post-traumatic stress disorder (PTSD). Yet, PTSD patients who received successful exposure therapy are vulnerable to relapse of fear response after a period of time, a phenomenon known as spontaneous recovery (SR). Increasing evidence suggests ventral hippocampus, basolateral amygdala, and infralimbic cortex may be involved in SR. PTSD patients also show high rates of comorbidity with nicotine dependence. While the comorbidity between smoking and PTSD might suggest nicotine may alter SR, the effects of nicotine on SR of contextual fear are unknown. In the present study, we tested the effects of acute nicotine administration on SR of extinguished contextual fear memories and c-fos immediate early gene immunohistochemistry in mice. Our results demonstrated that acute nicotine enhanced SR of extinguished fear whereas acute nicotine did not affect retrieval of unextinguished contextual memories. This suggests that the effect of acute nicotine on SR is specific for memories that have undergone extinction treatment. C-fos immunoreactive (IR) cells in the ventral hippocampus and basolateral amygdala were increased in the nicotine-treated mice following testing for SR, whereas the number of IR cells in the infralimbic cortex was decreased in the same group. Overall, this study suggests that nicotine may adversely affect context-specific relapse of fear memories and this effect is potentially mediated by the suppression of cortical regions and increased activity in the ventral hippocampus and amygdala.

Original languageEnglish (US)
Pages (from-to)405-414
Number of pages10
JournalLearning and Memory
Issue number8
StatePublished - Aug 2016


All Science Journal Classification (ASJC) codes

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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