Doxorubicin-induced sweet taste sensitivity reduction and compensatory receptor expression in mice

In cancer chemotherapy, the development of taste disorders is a serious problem because it not only reduces quality of life but also deteriorates patients' nutritional status, sometimes resulting in cessation of chemotherapy. Doxorubicin (DOX), a widely used anticancer anthracycline, reportedly alters patients' taste perception. However, little information exists on the detailed characteristics of DOX-induced taste disorders. In this study, we investigated whether taste responsiveness was altered in DOX-administered mice using a brief-access test and examined the underlying mechanisms. DOX-administered mice exhibited decreased responsiveness to sweet taste, but not to umami, bitter, salty, or sour tastes, on day 7, with recovery by day 14. Although there was no detectable alteration in the number of type II-taste cell marker-immunoreactive cells in the circumvallate papillae (CP), expression of mRNA for sweet taste receptors T1R2, T1R3, and α-gustducin in the CP was greater in DOX-administered mice than in control mice on day 7. Interestingly, in DOX-administered mice on day 7, the lick ratios for a 300-mM sucrose solution showed a significant correlation with the relative expression of T1R3 mRNA in the CP and a trend toward a correlation with food consumption. Together, these findings suggest that the decrease in sweet taste sensitivity in DOX-administered mice might result from dysfunction in signaling downstream of taste perception, with increased sweet taste receptor expression potentially representing a compensatory response to decreased energy intake.