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

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2019-11, Vol.43 (11), p.2421-2430
• Main Authors: Houck, Christa A., Carron, Claire R., Millie, Lauren A., Grahame, Nicholas J.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol Drinking - adverse effects; Alcohol Drinking - drug therapy; Alcohol Drinking - psychology; Alcohol use; Alcoholic beverages; Alcoholism; Alcohols; Animals; Aversion; Disease Models, Animal; Drinking; Drinking behavior; Drug abuse; Ethanol; Experiments; Female; Inbreeding; Male; Mice; Quinine; Quinine - pharmacology; Quinine Resistance; Rodents; Saccharin; Saccharin - pharmacology; Selectively Bred; Yield
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14196

Background 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. Methods 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. Results 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. Conclusions 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. Alcoholics drink in spite of negative consequences, a behavior which may be modeled in animals by adding quinine to alcohol. Here selectively bred cHAP mice, which voluntarily consume alcohol to BACs of over 200 mg/dl, drank 10% alcohol with added quinine. Five weeks of drinking (5W) causes escalation of drinking (*), but even naïve mice (0W) show quinine resistance at lower concentrations. In other experiments, we show tha