Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice

Behav Brain Res. 2008 Jul 19;190(2):174-81. doi: 10.1016/j.bbr.2008.02.018. Epub 2008 Feb 20.

Abstract

Nicotine withdrawal is associated with multiple symptoms such as anxiety, increased appetite, and disrupted cognition in humans. Although animal models have provided insights into the somatic and affective symptoms of nicotine withdrawal, less research has focused on the effects of nicotine withdrawal on cognition. Therefore, in this study, C57BL/6J mice were used to test the effects of withdrawal from chronic nicotine on foreground and background contextual fear conditioning, which present the context as a primary or secondary stimulus, respectively. Mice withdrawn from 12 days of chronic nicotine (6.3mg/kg/day) or saline were trained and tested in either foreground or background contextual fear conditioning; nicotine withdrawal-associated deficits in contextual fear conditioning were observed in both conditions. Mice were also tested for the effects of withdrawal on pre-pulse inhibition of the acoustic startle reflex (PPI), a measure of sensory gating, and on the acoustic startle reflex. Mice withdrawn from 12 days of chronic nicotine (6.3 or 12.6 mg/kg/day) or saline underwent one 30-min PPI and startle session; no effect of withdrawal from chronic nicotine on PPI or startle was observed for either dose at 24h after nicotine removal. Therefore, mice were tested at different time points following withdrawal from 12.6 mg/kg/day chronic nicotine (8, 24, and 48 h after nicotine removal). No effect of withdrawal from chronic nicotine was observed at any time point for PPI. Overall, these results demonstrate that nicotine withdrawal disrupts two methods of contextual learning but not sensory gating in C57BL/6J mice.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation
  • Analysis of Variance
  • Animals
  • Association Learning / drug effects*
  • Attention / drug effects*
  • Conditioning, Classical / drug effects
  • Dose-Response Relationship, Drug
  • Fear / drug effects
  • Inhibition, Psychological
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Perception / drug effects
  • Reflex, Startle / drug effects*
  • Signal Transduction / drug effects
  • Substance Withdrawal Syndrome / physiopathology*
  • Time Factors

Substances

  • Nicotinic Agonists
  • Nicotine