Nicotine sensitization (Part 2): Time spent in the centre of an open field sensitizes to repeated nicotine into the drug-free state in female rats

Rationale Nicotine is initially anxiogenic and becomes anxiolytic after prolonged exposure. The mechanisms that facilitate the shift in anxiety-like behaviour produced by nicotine are unclear. Objective We investigated the change in time spent in the centre of an open field (as a measure anxiety-like behaviour) produced by three intermittent injections of nicotine as part of experiments of locomotor sensitization to nicotine. Methods Rats were injected with nicotine (0.4 mg/kg) or saline and immediately placed in the open field arena for 1 h on two consecutive days and again 9 days later. Results When given saline, time spent in the centre of the arena did not change, whereas repeated nicotine injections increased in time spent in the centre beyond the increase produced by an acute injection of nicotine. Repeated nicotine (and not acute nicotine) also increased time in the centre in a drug-free state when tested 24 h after the last injection. Conclusion Repeated nicotine sensitized the time spent in the centre of an open field with the long-lasting sensitization of this measure of anxiety-like behaviour evident in a drug-free state, in contrast to locomotor sensitization which does not persist in the drug-free state. The results suggest independence of the mechanisms of sensitization that underlie locomotor and anxiolytic effects.