Innate and acquired tolerance to bitter stimuli in mice.

Emi Mura,Yukako Hayashi,Akiyuki Taruno,Kohei Yokota,Minako Yagi,Maik Behrens

doi:10.1371/journal.pone.0210032

Emi Mura, Yukako Hayashi + Show 4 more

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https://doi.org/10.1371/journal.pone.0210032

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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.

Highlights

Bitter taste is generally considered a signal to avoid the ingestion of potentially toxic compounds; the rejection of bitter-tasting foods is crucial for survival because many toxic compounds taste bitter
They are wellknown bitter compounds for humans and TAS2R4 is a target of L-tryptophan, whereas the receptor for L-isoleucine is unknown
Two questions were addressed in mice: (1) whether there is an acceptable range of the bitter stimulus intensity for various bitter compounds, and (2) whether prolonged experience of a benzoate Quinine-HCl

Summary

Introduction

Bitter taste is generally considered a signal to avoid the ingestion of potentially toxic compounds; the rejection of bitter-tasting foods is crucial for survival because many toxic compounds taste bitter. Bitter rejection is an innate response commonly seen in mammals, demonstrated by the fact that human infants and other mammals show hedonically negative facial expressions in response to bitter taste stimuli [1–4]. Bitter sensation does not always evoke aversive responses. Acceptance of bitterness is commonly noted for certain foods such as vegetables, and it may be modulated by experience [5].

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