CD-1 mice show individual differences in nicotine preference in a modified two-bottle oral self-administration model

Abstract

Although both animal and human studies reveal significant contributions of genetics to smoking addiction, many human studies were underpowered or biased by potential confounding variables, and animal genetic studies are challenged by limited genetic variations and lack of convincing phenotypes. To address these concerns, we used non-sibling outbred CD-1 mice to evaluate individual differences in nicotine preference with 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. Under this regular two-bottle choice condition, the majority of animals avoided the nicotine solution with limited individual differences. However, when we modified the model by introducing 4 days of exposure to 5% saccharin in the drinking water, the animals significantly increased nicotine consumption in the two-bottle choice test, with about 30% animals showing a nicotine preference. Nicotine preference after 5% saccharin treatment remained elevated throughout the 28 days of the experiment. Further, we found there existed striking individual differences in nicotine consumption after exposure to 5% saccharin, with a range of 0–100% of total liquid consumption. The enhanced individual differences and the ratio of nicotine consumption were observed at different concentrations of nicotine (10–80 μg/ml) and in both adolescents and adults. Further examination on the induction mechanism showed that the long-lasting nicotine preference was not correlated with nicotine consumption before the induction, 5% saccharin consumption, or weight gain during the induction. Although liquid consumption during the 4 days of 5% saccharin exposure was decreased by about 30%, comparable liquid restriction alone for 4 days did not induce nicotine preference. Together, this study showed a strong and stable nicotine preference in CD-1 mice, which was induced by a short-term high concentration of saccharin in the drinking water. Considering the nature and heterogeneity of CD-1 mice, the striking individual differences imply that genetics plays an important role in nicotine preference observed in these animals.

Midazolam, methamphetamine, morphine and nicotine intake in high‐drinking‐in‐the‐dark mice

“…However, it should be noted that behavioural effects of nicotine can vary markedly by genotype 74 . The concentrations selected for testing in this experiment are consistent with other published work on nicotine drinking in mice, 39–41 and voluntary intake levels of nicotine in the HDID‐2 mice are similar to those of C57BL/6 mice in limited‐access procedures 39 . Interestingly, genotype effects have emerged for nicotine‐induced conditioned taste aversion, with C57BL/6J mice showing a relative insensitivity to the aversive effects of nicotine relative to the DBA/2J, BALB/cJ and C3H/HeJ strains 75 .…”

“…All solutions were prepared daily and transferred into 10‐ml tubes, each fitted with a metal sipper and a ball bearing for drinking procedures. Drug concentrations were determined from previous studies of drinking behaviour in mice, when available 25,26,39–43 …”

Full-Length Human Placental sFlt-1-e15a Isoform Induces Distinct Maternal Phenotypes of Preeclampsia in Mice

“…However, this maternal liver disease probably sensitized this animal to any hsFlt-1-e15a effect, and promoted the development of a more severe and fulminant preeclampsia phenotype with heightened and early blood pressure elevation, generalized endothelial dysfunction, and generalized thrombotic disease, which affected the liver and the placenta, and led to consequent fetal growth restriction. We could not investigate maternal coagulation status in this mouse because we did not obtain maternal plasma specimens; however, since CD-1 is an outbred mouse strain with individual animals having a different genetic background [ 273 – 275 ], we hypothesize that the “EM35” mouse might have had a thrombotic disorder. This finding is consistent with the observation that inherited and acquired thrombophilias predispose for the development of severe preeclampsia and early-onset preeclampsia in humans [ 276 – 279 ], and also that women developing early-onset preeclampsia may have a pre-existing metabolic disease [ 22 , 280 ].…”

Individual differences in the behavioral effects of nicotine: A review of the preclinical animal literature

“…A study examining the interaction between pre-pulse inhibition and locomotor sensitization found that low inhibitory rats (i.e., rats that had lower pre-pulse inhibition scores) were more prone to developing nicotine sensitization (Kayir et al, 2011). Additionally, there are a number of reports using an individual rodent's nicotine consumption or self-administration behavior as a data analysis tool (Adriani et al, 2002; Cao et al, 2012; Dadmarz and Vogel, 2003; Harris et al, 2009; Harris et al, 2011; Maehler et al, 2000; Nesil et al, 2011). These techniques bear mentioning here as they may be used in conjunction with other models to give more information about the individual rodents which have a higher reactivity to nicotine.…”