AUTHOR=Cao Junran , Gautier Nicole M., Li Ming D.

TITLE=CD-1 Mice Show Individual Differences in Nicotine Preference in a Modified Two-Bottle Oral Self-Administration Model

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 3 - 2012

YEAR=2012

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2012.00028

DOI=10.3389/fpsyt.2012.00028

ISSN=1664-0640

ABSTRACT=Genetic epidemiology reveals significant contributions of genetics to smoking addiction. However, such study is underpowered because of the many potential confounding variables. These issues can be compensated for by a proper animal model.  In the current study, we used non-sibling CD-1 mice to increase the genetic variation and evaluated nicotine preference in a modified two-bottle oral self-administration model. Animals were first given free access to two bottles, one filled with nicotine dissolved in 2% saccharin and the other with saccharin only.  At this stage, the majority of animals avoided the nicotine solution with small individual differences. However, after four days of exposure to 5% saccharin in the drinking water, the ratio of nicotine consumption to total liquid consumption was significantly increased, and about 40% animals showed a nicotine preference. There were striking individual differences in nicotine consumption, with a range of 0 to 100% of total liquid consumption. Nicotine preference after 5% saccharin treatment remained elevated throughout the 28 days of experiment. The enhanced ratio of nicotine consumption and individual differences were observed at different concentrations of nicotine (10 to 80 µg/ml) and in both adolescents and adults. Although liquid consumption during the four days of 5% saccharin induction was decreased by about 30%, comparable liquid restriction alone for four days did not induce nicotine preference. The long-lasting nicotine preference was not correlated with nicotine consumption before the induction, 5% saccharin consumption, or weight gain during the induction. Together, this study showed a long-lasting nicotine preference in CD-1 mice, which was induced by a short-term high concentration of saccharin in the drinking water. We observed significant individual differences in nicotine consumption. Given the nature and heterogeneity of CD-1 mice, such striking individual differences indicate that genetics plays an im