Effect of forced chronic oral nicotine exposure on intravenous self-administration and rewarding properties of acute nicotine

The effect of 7-week forced oral nicotine exposure on acquisition of intravenous nicotine self-administration, nicotine place conditioning, and nicotine preference was studied in mice. The nicotine solution was given in stepwise increased concentrations as the sole source of liquid for 7 weeks. Nicotine exposed animals self-administered nicotine intravenously at lower unit dose than nicotine-naïve ones, indicating that the forced 7-week nicotine exposure, followed by 7-day withdrawal, had rendered them more sensitive to nicotine's reinforcing effects. At the dose of 0.5 mg/kg, nicotine induced conditioned place preference both in drug-naïve and nicotine exposed mice, but the 0.3 mg/kg dose of nicotine failed to do so. The forced nicotine pre-exposure did not alter the nicotine preference in the 2-bottle free-choice paradigm. In conclusion, these results suggest that nicotine pre-exposure enhances the reinforcing effects of acutely administered nicotine only in the intravenous self-administration model.