Innate and Acquired Quinine-Resistant Alcohol, but not Saccharin, Drinking in Crossed High-Alcohol-Preferring Mice

Alcohol consumption despite aversive consequences is often a key component of an alcoholism diagnosis. Free-choice alcohol consumption despite bitter quinine adulteration in rodents has been seen following several months of free-choice drinking, but there has been little study of whether prolonged access to other palatable substances such as saccharin yields quinine resistance. Selectively bred crossed high-alcohol-preferring (cHAP) mice average blood alcohol levels of over 250 mg/dl during free-choice access, considerably higher than other models. We hypothesized that higher intakes would yield more rapid development of quinine-resistant alcohol (QRA) drinking and quinine-resistant saccharin (QRS) drinking.

All experiments used male and female cHAP mice. Experiment 1 compared mice with either 0 or 5 weeks of alcohol drinking history, testing varying (0.032, 0.10, 0.32 g/l) quinine concentrations in ethanol. Experiment 2 examined whether innate QR may exist, comparing animals with a 1 or zero day of drinking history. Experiment 3 examined the effect of varying histories (0, 2, or 5 weeks) of free-choice 10% alcohol drinking on QR alcohol consumption at high quinine concentrations. Finally, Experiment 4 investigated the development of QRS drinking.

We found that we could not detect a history effect in commonly used quinine concentrations, indicating that cHAP mice are innately quinine resistant to 0.10 g/l quinine. However, we were able to determine that a 2-week drinking history was sufficient to induce QRA drinking in cHAP mice at extremely high quinine concentrations (0.74 and 0.32 g/l). However, the history effect was specific to QRA, a saccharin drinking history, did not yield QRS drinking.

These data suggest that an alcohol drinking history induces maladaptive behaviors, such as drinking in spite of negative consequences, a pattern not seen with saccharin. Furthermore, a strong genetic predisposition to drink may promote an innate aversion resistance compared with commonly used inbred strains.