Restricted daily access to water and voluntary nicotine oral consumption in mice: methodological issues and individual differences.

Nicotine (NIC) shares most of the characteristics of other addictive drugs. However, attempts to establish oral self-administration failed under an ad libitum fluid availability. Outbred mice were scheduled to a restricted 2 h/day water access. In Experiment I, such schedule elevated corticosterone blood levels, which were strongly reduced following the drinking session. In two replications of Experiment II, mice had several days of free choice between water or NIC (10 mg/l). A consistent and reliable preference for NIC was found. Mice also progressively increased their drug intake in a fading study. In Experiment III, levels of cotinine (the principal NIC biomarker in the blood) confirmed pharmacologically active drug concentrations after oral intake. In Experiment IV, another set of mice was exposed to a 6-days 'passive' nicotine consumption, by masking the drug taste with 10% sucrose. After sucrose removal, a preference for NIC emerged, which however vanished during the following days. This 'neutral' profile resulted to be the combined performance of a NIC-preferring and a NIC-non-preferring subpopulations. In conclusion, a clear-cut preference for NIC can be easily established when the drug offer is concurrent to a restricted access to water. The present paradigm may be useful to investigate issues of NIC dependence.