Innate and acquired tolerance to bitter stimuli in mice

Abstract

Tolerance to bitter foods and its potentiation by repetitive exposure are commonly experienced and potentially underlie the consumption of bitter foods, but it remains unknown whether permissive and adaptive responses are general phenomena for bitter-tasting substances or specific to certain substances, and they have not been rigorously studied in mice. Here, we investigated the effects of prolonged exposure to a bitter compound on both recognition and rejection behaviors to the same compound in mice. Paired measurements of rejection (RjT) and apparent recognition (aRcT) thresholds were conducted using brief-access two-bottle choice tests before and after taste aversion conditioning, respectively. First, RjT was much higher than aRcT for the bitter amino acids L-tryptophan and L-isoleucine, which mice taste daily in their food, indicating strong acceptance of those familiar stimuli within the concentration range between RjT and aRcT. Next, we tested five other structurally dissimilar bitter compounds, to which mice were naive at the beginning of experiments: denatonium benzoate, quinine-HCl, caffeine, salicin, and epigallocatechin gallate. RjT was moderately higher than aRcT for all the compounds tested, indicating the presence of innate acceptance to these various, unfamiliar bitter stimuli in mice. Lastly, a 3-week forced exposure increased RjT for all the bitter compounds except salicin, demonstrating that mice acquire tolerance to a broad array of bitter compounds after long-term exposure to them. Although the underlying mechanisms remain to be determined, our studies provide behavioral evidence of innate and acquired tolerance to various bitter stimuli in mice, suggesting its generality among bitterants.

Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits

“…AgRP neuron stimulation did not affect EtOH intake but robustly increased glucose intake (Figures 2N and 2O). This is not likely due to the unpleasant taste of alcohol, as mice drank glucose that was devalued with an aversive concentration of quinine (0.3 mM, Figure 2P) (Grobe and Spector, 2008;Mura et al, 2018). If mice calculate the caloric value of alcohol, one prediction would be that they consume less of a glucose/EtOH mixture (0.32 kcal/mL, 0.16 kcal/mL from glucose, and 0.16 kcal/mL from EtOH) compared to just glucose (0.16 kcal/mL).…”

“…Mice were attached to patch fiber and lasers with access to either 8% glucose or 8% glucose with 0.3 mM quinine in a counterbalanced experimental design. This concentration of quinine reduces preference by approximately 50% in rats and mice (Grobe and Spector, 2008;Mura et al, 2018). Glucose and glucose/quinine intake were recorded after a 1-h baseline, and again after 1 h of AgRP neuron stimulation.…”

Change in Taste Preference to Capsaicin and Catechin Due to Aging in Mice

“…Notably, the catechin mixture contained caffeine (0.8%). As B6 mice show avoidance behavior towards .1 mM caffeine (18), we consider that the caffeine present in our catechin solutions (approximately 1 to 40 mM) did not have a significant effect on the avoidance behavior shown towards them.…”

Intranasal Administration of Rotenone Reduces GABAergic Inhibition in the Mouse Insular Cortex Leading to Impairment of LTD and Conditioned Taste Aversion Memory

“…After the recovery, water-deprived mice for 16 h were trained for two days to perform brief-access licking of distilled water through a single drinking bottle for no more than 2 s. On the next day, the mice were presented with 0.03 mM quinine hydrochloride (QHCl; Nacalai Tesque, Kyoto, Japan) solution for 10 min, and the amount consumed from a single drinking bottle was measured to test innate aversiveness to 0.03 mM QHCl. The dose of QHCl was set near the aversion threshold in naive animals [ 59 ]. On the next two days, the paring of conditioned stimulus (CS) with the unconditioned stimulus (US) was repeated.…”