Developmental effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning

George S. Portugal, Derek S. Wilkinson, Jill R. Turner, Julie A. Blendy, Thomas J. Gould

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, such as changes in nicotinic acetylcholine receptor (nAChR) binding, CREB expression, and nicotine metabolism. Age-related differences existed in sensitivity to the effects of acute nicotine, chronic nicotine and nicotine withdrawal on contextual fear conditioning (no changes in cued fear conditioning were seen); younger mice were more sensitive to the acute effects and less sensitive to the effects of nicotine withdrawal 24. h post treatment cessation. Developmental differences in nAChR binding were associated with the effects of nicotine withdrawal on contextual learning. Developmental differences in nicotine metabolism and CREB expression were also observed, but were not related to the effects of nicotine withdrawal on contextual learning 24. h post treatment. Chronic nicotine exposure during pre-adolescence or adolescence, however, produced long-lasting impairments in contextual learning that were observed during adulthood, whereas adult chronic nicotine exposure did not. These developmental effects could be related to changes in CREB. Overall, there is a developmental shift in the effects of nicotine on hippocampus-dependent learning and developmental exposure to nicotine results in adult cognitive deficits; these changes in cognition may play an important role in the development and maintenance of nicotine addiction.

Original languageEnglish
Pages (from-to)482-494
Number of pages13
JournalNeurobiology of Learning and Memory
Issue number4
StatePublished - May 2012

Bibliographical note

Funding Information:
The authors would like to acknowledge grant support from the National Institute on Drug Abuse (DA017949 TG; DA024787 TG), and the National Cancer Institute (CA143187 PI: Caryn Lerman PhD), and thank Dr. Randy James of Virginia Commonwealth University for his analysis of plasma samples.


  • Acetylcholine
  • Addiction
  • Adolescent
  • Hippocampus
  • Learning

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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