The Effect of Acute Nicotine Administration on Human Delay Cued and Context Fear Conditioning

Alexandra N. Palmisano, Thomas J. Gould, Robert S. Astur

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Nicotine has been shown to facilitate hippocampal-dependent context fear conditioning (FC), but not hippocampal-independent delay cued fear conditioning. Studies examining the effects of nicotine on learned fear have been exclusively limited to nonhumans. The present study aimed to translate nonhuman findings by investigating the effects of nicotine on cued and context fear in humans using a virtual reality (VR) analog of the fear conditioning task. Sixty-seven nicotine-using undergraduates were randomly assigned to receive either a 2 mg nicotine or placebo lozenge prior to conditioning. During conditioning, participants were confined to a virtual room and were conditioned to green floodlight presentations (conditioned stimulus [CS+]) paired with a wrist shock (unconditioned stimulus [US]).A red floodlight served as the CS− during which no shock occurred. Delay cued and context fear testing immediately followed conditioning. Physiological skin conductance responses (SCRs) were recorded continuously throughout all sessions. Nicotine enhanced context fear conditioning such that SCRs to the shock-paired context were significantly greater for the nicotine group than the placebo group. Nicotine did not enhance delay cued fear. Exploratory analyses examining the relationship between fear conditioning and self-reported anxiety revealed that relative to those with lower levels of trait anxiety, nicotine-treated individuals with higher trait anxiety levels were less likely to demonstrate differential conditioning to the shock-paired cue. These findings support abundant nonhuman literature indicating that nicotine facilitates hippocampus-dependent versions of fear conditioning in humans. Results also suggest a role for dysregulated safety learning in pathological anxiety, which may be exacerbated by nicotine use.

Original languageEnglish (US)
Pages (from-to)464-474
Number of pages11
JournalExperimental and clinical psychopharmacology
Issue number2
StatePublished - Sep 8 2022

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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