Pharmacologic characterization of nicotine-induced conditioned place preference.

Rats received subcutaneous injections of either nicotine (0.1 to 1.2 mg/kg) or saline (1.0 ml/kg) immediately prior to conditioning sessions in a conditioned place preference (CPP) paradigm. The drug was paired for 3 conditioning sessions with the non-preferred environment of a 3 compartment place preference apparatus; saline was paired with the preferred environment. The animals were then tested for place preference by determining the proportion of time spent in the preferred and non-preferred compartments during a 15 min test session. Using a statistical method developed for the CPP paradigm, dose-response curves were obtained for the rewarding and aversive effects of nicotine as measured by its ability to alter previously determined baseline preferences obtained from the control animals. Nicotine's rewarding and aversive effects were linearly correlated with respect to dosage within the range of 0.1-0.8 mg/kg (reward increased and aversion decreased). A decrease in reward and an increase in aversion was measured at the 1.2 mg/kg treatment level. Mecamylamine hydrochloride and hexamethonium bromide (at 1.0 mg/kg of the base or ion, respectively) were also tested using the CPP paradigm. While neither compound produced place preferences when administered alone, mecamylamine did block the rewarding effects of 0.8 mg/kg of nicotine when administered 30 minutes prior to the nicotine conditioning sessions. Hexamethonium did not alter nicotine-induced reinforcement. The data suggest that nicotine and its rewarding effects as measured by CPP are primarily mediated by central rather than peripheral events.