Preference for nicotine and quinine in mice. (A) Preference for 1 mM nicotine was measured in 2-bottle tests vs. water (9 KO and 10 WT) and vs. 10 mM quinine (9 KO and 9 WT). With the exception of WT mice, that preferred nicotine to quinine, nicotine was always aversive (***, P < 0.0001, independent 1-sample t tests vs. 0.5, Bonferroni–Holm's; dashed line at the 0.5 indifference ratio). Accordingly, significant effects on preference were found for genotype, reference tastant and their interaction (P < 0.0001 for all; 2-way ANOVA) with differences between genotypes only when nicotine was tested against quinine (P < 0.001, Bonferroni). (B) The preference for 0.5 and 1 mM nicotine vs. water was tested in two bottle tests run in 9 KO and 9 capsaicin-treated KO mice. Nicotine was aversive in both groups of animals (*, P < 0.04; **, P < 0.004; ***, P < 0.0008) and treatment, concentration or their interaction had no effects on preference (P > 0.5, P > 0.2 and P > 0.1; 2-way repeated measures ANOVA).