Nicotine enhancement of contextual fear conditioning

Abstract

Nicotine has been suggested to have cognitive enhancing effects. The present study examined the effects of nicotine and the nicotinic antagonist mecamylamine on contextual fear conditioning in C57BL/6 mice. The fear conditioning task was chosen because the task examines two types of learning: contextual learning, and conditioned stimulus (CS)–unconditioned stimulus (US) learning. Multiple doses of nicotine were tested and 0.5 mg/kg nicotine, given on both training and testing days, improved contextual learning but had no effect on formation of an auditory CS–US association. No effect was found at lower doses or when nicotine was given on training day only, or testing day only. The nicotinic receptor antagonist mecamylamine (1 and 2 mg/kg) did not alter contextual fear conditioning but mecamylamine did prevent the nicotine-associated increase in contextual learning. A higher dose of nicotine (1 mg/kg, training day only) interfered with contextual conditioning when the context was paired with both the CS and US, but had no effect on the auditory CS–US association. This effect of 1 mg/kg nicotine on contextual learning disappeared when mice were trained without the CS. The present results indicate that nicotine enhancement of contextual fear conditioning is dose-dependent, but the presence of nicotine is required both during training and testing.