Nicotine induces conditioned place preferences over a large range of doses in rats

Rationale: Conditioned place preference (CPP) procedures provide one measure of potential rewarding effects of abused drugs. Many attempts to induce CPP with nicotine have been unsuccessful. Objectives: To assess the influence of nicotine dose and stimulus assignment procedure on development of nicotine-induced CPP. Methods: Initial preferences for one side of a two-compartment apparatus were first determined in Sprague-Dawley rats. In subsequent conditioning trials, the compartment paired with nicotine was the initially preferred side for half of the rats, and the initially nonpreferred side for the other half. Rats received either an injection of nicotine (0.01-2 mg/kg SC) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials). Control rats had saline injections associated with both compartments. A final test trial with no injection assessed final place preference. Results: Significant CPP were induced by 0.1-1.4 mg/kg doses of nicotine. Nicotine-induced CPP were only apparent when nicotine was paired with the intially non-preferred side. Moreover, a very high dose of nicotine (2 mg/kg) induced conditioned place aversion when paired with the initially preferred side of the apparatus. Conclusions: Nicotine induced significant CPP across a wide range of doses, in accordance with its role as the primary addictive component of tobacco. Small preferences for one side of the apparatus played a major role in the development of nicotine-induced CPP. These findings suggest that biased procedures may be more Suitable than unbiased procedures for evaluation of rewarding effects of nicotine using CPP paradigms.