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

Abstract

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.

Absolute ethanol intake predicts ethanol preference inDrosophila

“…Human studies of ethanol drinking initiation distinguish between the experiences of the first drink and the first intoxicationwhich often do not coincideon their effect on drinking habits in adulthood (Samson, 1987). We speculate that consumptive ethanol preference in Drosophila similarly depends on suprathreshold substance intake, as shown in studies of self-administered oral preference for drugs of abuse in rodents (Grim et al, 2018). This explanation is consistent with previous reports that ethanol preference increases with the duration and intensity of exposure (Devineni and Heberlein, 2009; Peru Y. Colón de Portugal et al, EtOH, ethanol; PI, preference index; S, sucrose; T, tryptone.…”

“…Human studies of ethanol drinking initiation distinguish between the experiences of the first drink and the first intoxication-which often do not coincide-on their effect on drinking habits in adulthood (Samson, 1987). We speculate that consumptive ethanol preference in Drosophila similarly depends on suprathreshold substance intake, as shown in studies of self-administered oral preference for drugs of abuse in rodents (Grim et al, 2018). This explanation is consistent with previous reports that ethanol preference increases with duration and intensity of exposure Heberlein, 2009, Peru Y. Colón de Portugal et al, 2014) and that ethanol preference is attenuated or abolished when the CAFE vials are supplemented with additional food source (Park et al, 2018)-which would effectively decrease overall consumption of the test diets and thus the mixed-in ethanol, making it less likely for animals to ingest enough ethanol to meet the threshold for establishing preference.…”

A Novel Morphine Drinking Model of Opioid Dependence in Rats

“…On the other hand, when quinine is included in the alternative bottle, a preference for the morphine solution is observed, suggesting that quinine is effective in driving morphine consumption and generating dependence. However, several reports demonstrated that, in this paradigm, high morphine preference is not related to the rewarding properties of the drug, but its preference is influenced by the degree of quinine aversion [ 15 , 16 ]. Thus, it was postulated that the aversion to the bitter taste of quinine is what leads to the maintenance of relatively high levels of fluid consumption from the morphine bottle [ 15 ].…”

Chronic Sleep Deprivation Blocks Voluntary Morphine Consumption but Not Conditioned Place Preference in Mice

“…Therefore, we used a two-bottle choice method for administering morphine. Our method used a 0.2% saccharin solution in both the morphine and vehicle bottles, which generally produces a morphine preference in C57Bl6/J mice ( Belknap et al, 1993 ), and avoids the confound of quinine influencing choice consumption more than morphine ( Grim et al, 2018 ). We used an established model of CSS ( Zhu et al, 2018 ) with non-invasive sleep (behavioral quiescence) recording and automated drinking sensors to assess the effect of prolonged sleep disturbance on both voluntary consumption and associative rewarding properties of morphine in male mice.…”