Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli

Abstract

Background: Common inbred mouse strains are genotypically diverse, but it is still poorly understood how this diversity relates to specific differences in behavior. To identify quantitative trait genes that influence taste behavior differences, it is critical to utilize assays that exclusively measure the contribution of orosensory cues. With a few exceptions, previous characterizations of behavioral taste sensitivity in inbred mouse strains have generally measured consumption, which can be confounded by post-ingestive effects. Here, we used a taste-salient brief-access procedure to measure taste sensitivity to eight stimuli characterized as bitter or aversive in C57BL/6J (B6) and DBA/2J (D2) mice.

Results: B6 mice were more sensitive than D2 mice to a subset of bitter stimuli, including quinine hydrochloride (QHCl), 6-n-propylthiouracil (PROP), and MgCl2. D2 mice were more sensitive than B6 mice to the bitter stimulus raffinose undecaacetate (RUA). These strains did not differ in sensitivity to cycloheximide (CYX), denatonium benzoate (DB), KCl or HCl.

Conclusion: B6-D2 taste sensitivity differences indicate that differences in consumption of QHCl, PROP, MgCl2 and RUA are based on immediate orosensory cues, not post-ingestive effects. The absence of a strain difference for CYX suggests that polymorphisms in a T2R-type taste receptor shown to be differentially sensitive to CYX in vitro are unlikely to differentially contribute to the CYX behavioral response in vivo. The results of these studies point to the utility of these common mouse strains and their associated resources for investigation into the genetic mechanisms of taste.

Figure 1

Concentration-response functions quinine in 10 individual B6 mice. Data points for each mouse represent average ratios across two days of testing; these means were fitted with two-parameter logistic functions and the concentration evoking half-maximal avoidance, c, was estimated. Italicized mice (B103, B96, B93, B67) were given QHCl as the last of three stimuli, as opposed to the others, which received QHCl as the first stimulus.

Figure 2

Concentration-response functions for QHCl in 10 individual D2 mice. Data points for each mouse represent average ratios across two days of testing; these means were fitted with two-parameter logistic functions and the concentration evoking half-maximal avoidance, c, was estimated. For one mouse (D98) this parameter could not accurately estimated, although this mouse had a mean lick ratio of 0.52 for 1 mM QHCl. Italicized mice (D81, D82, D53, D57, D58) were given QHCl as the last of three stimuli, as opposed to the others which received QHCl as the first stimulus.

Figure 3

Lick ratios (mean ± SE) for B6 and D2 mice to concentration series of QHCl (A), PROP (B), MgCl₂ (C), and RUA (D). The dotted lines on each graph represent a ratio score of 1.0, which indicates a lick rate equal to that of water. Asterisks identify significant strain effects at particular concentrations, as indicated by planned comparisons (p < 0.01). Lick ratios for each strain generally decreased with increasing concentration; B6 made fewer licks than D2 mice to high concentrations of QHCl (A) and PROP (B), and to both low and concentrations of MgCl₂ (C). D2 mice made fewer licks than B6 mice at almost all concentrations of RUA (D).

Figure 4

Lick ratios (mean ± SE) for B6 and D2 mice to concentration series of CYX (A), DB (B), KCl (C), and HCl (D). The dotted lines on each graph represent a ratio score of 1.0, which indicates a lick rate equal to that of water. Lick ratios for each strain decreased with increasing concentration. The strains did not differ significantly for any of these compounds.

Figure 5

Strain comparison of latency to initiate taste trials of all eight stimuli. W = water trials. Latencies are means (± SE) of the median latencies for individual mice. A significant strain difference was found only for KCl. Effects of concentration were found for DB and HCl.