We further evaluated whether the anorectic effect of nicotine was associated with an aversive response by performing a CTA experiment. In this type of experiment a saccharin preference ratio <50% was considered a marker of CTA, since it indicates that rats prefer to drink water after an aversive response to saccharine (26). LiCl was used as a positive control, and as expected, LiCl-treated rats drank significantly less saccharin solution (LiCl paired flavor; Fig. 1D), indicating that they had developed CTA (26). Vehicle and nicotine-treated rats had a similar saccharine preference consumption ratio, and it is noteworthy that this was >50% (Fig. 1D). Supporting the absence of stress, illness, or malaise associated with the nicotine treatments, we did not observe reduced LA (Fig. 1G), changes in skin aspect, stool consistency, or obvious abnormal behavior such as was evident in the LiCl-treated animals (data not shown) (26).
