The effect of quinine in two bottle choice procedures in C57BL6 mice: Opioid preference, somatic withdrawal, and pharmacokinetic outcomes.

Previous reports assessing morphine effects in two bottle choice (TBC) paradigms often use taste adulterants such as sweeteners (e.g., saccharin) and/or bitterants (e.g., quinine) to demonstrate morphine preference with C57BL6 mice. The effect of these additional components on the morphine preference of C57BL6 remains poorly understood. Thus, we sought to elucidate the interrelationship of morphine and quinine in the TBC paradigm. As expected, when morphine was included in the opposite bottle from quinine, a preference for the morphine solution was observed. Conversely, when quinine was included in each bottle, or when fentanyl without quinine was used, no preference was observed. All opioid-drinking mice displayed withdrawal signs, and morphine was detectable in plasma and brain. When these results were compared to previous results via conversion to quinine preference scores, quinine was revealed to determine largely the measured morphine preference. Thus, quinine is effective to drive morphine consumption and engender dependence but may confound the ability to measure oral abuse liability of morphine. Together, these results suggest future TBC procedures should consider the effect of quinine upon measured preference for compounds in the opposite bottle, and that excessively high quinine concentrations appear to influence preference more so than the opposite solute when using C57BL6 mice. Alternative conditions to assess oral abuse liability may be necessary to complement and confirm results from TBC experiments utilizing morphine or other opioids.