Nicotine-conditioned locomotor sensitization in rats: assessment of the US-preexposure effect.

In rats, stimulus-nicotine associations can be altered by preexposure to the nicotine US (unconditioned stimulus). This alteration differs with the conditioning preparation. In a conditioned taste avoidance preparation, preexposure to nicotine weakens conditioning. In contrast, nicotine preexposure enhances acquisition of a nicotine-conditioned place preference. No one has examined the effects of US preexposure on nicotine locomotor conditioning. In three separate experiments, we assessed the effects of nicotine preexposure on the subsequent expression of conditioned hyperactivity produced by a nicotine US. We found evidence for nicotine-conditioned locomotor sensitization in non-preexposed rats that received repeated pairings of a distinct context with the psychomotor effects of a 0.42 mg/kg dose of nicotine (free base). Conditioning was not observed at lower nicotine doses (0.18 and 0.11 mg/kg) in non-preexposed rats. Preexposure to the 0.42 and 0.18 mg/kg doses of nicotine (3 or 9 days) attenuated acute locomotor suppression and enhanced the development of locomotor sensitization to that same dose. Despite similar qualitative shifts in the locomotor profile induced by preexposure to the nicotine US, conditioned hyperactivity was only altered after 3 or 9 days of preexposure at the 0.18 mg/kg dose. Thus, similar to place conditioning, nicotine preexposure can enhance the subsequent effectiveness of the nicotine US in a locomotor conditioning preparation.