Acute nicotine delays extinction of contextual fear in mice

Abstract

Smoking is linked to post-traumatic stress disorder (PTSD) which suggests smoking is either a risk factor or an attempt at self-medication. The ability to reduce or extinguish fear-related memories may be altered in patients with PTSD and it is possible that nicotine modulates this. Although there are numerous studies examining the effects of nicotine on acquisition of fear learning, the effects of nicotine on extinction of contextual fear are not well understood. In the present study, we examined the effects of acute nicotine (0.18 mg/kg) on extinction of contextual fear in C57BL/6J mice. Animals were first trained in a background contextual fear conditioning paradigm using a white noise as a conditioned stimulus (CS), which co-terminated with a 2 s 0.57 mA unconditioned foot-shock stimulus (US). Animals were then administered either nicotine or saline and exposed to either the training context or a novel context in order to measure freezing to the context during extinction. Our results demonstrate that nicotine administration during extinction delays extinction of contextual freezing while nicotine did not affect cued freezing or freezing to the novel context.

Keywords: Anxiety; Context; Extinction; Fear Conditioning; Nicotine; PTSD.