Zukerman S, Glendinning JI, Margolskee RF, Sclafani A. T1R3 taste receptor is critical for sucrose but not Polycose taste. In addition to their well-known preference for sugars, mice and rats avidly consume starch-derived glucose polymers (e.g., Polycose). T1R3 is a component of the mammalian sweet taste receptor that mediates the preference for sugars and artificial sweeteners in mammals. We examined the role of the T1R3 receptor in the ingestive response of mice to Polycose and sucrose. In 60-s two-bottle tests, knockout (KO) mice preferred Polycose solutions (4 -32%) to water, although their overall preference was lower than WT mice (82% vs. 94%). KO mice also preferred Polycose (0.5-32%) in 24-h two-bottle tests, although less so than WT mice at dilute concentrations (0.5-4%). In contrast, KO mice failed to prefer sucrose to water in 60-s tests. In 24-h tests, KO mice were indifferent to 0.5-8% sucrose, but preferred 16 -32% sucrose; this latter result may reflect the post-oral effects of sucrose. Overall sucrose preference and intake were substantially less in KO mice than WT mice. However, when retested with 0.5-32% sucrose solutions, the KO mice preferred all sucrose concentrations, although they drank less sugar than WT mice. The experience-induced sucrose preference is attributed to a post-oral conditioned preference for the T1R3-independent orosensory features of the sugar solutions (odor, texture, T1R2-mediated taste). Chorda tympani nerve recordings revealed virtually no response to sucrose in KO mice, but a near-normal response to Polycose. These results indicate that the T1R3 receptor plays a critical role in the tastemediated response to sucrose but not Polycose.preference; C57BL/6J mice; chorda tympani nerve; saccharin; postoral conditioning THE TASTE OF SUGAR IS HIGHLY attractive to humans and many other animal species. Studies of inbred mouse strains led to the identification of the T1R2 and T1R3 receptor proteins that dimerize to form a sweet taste receptor (1). Selective elimination of these receptor proteins in knockout mice attenuates or completely blocks the behavioral and gustatory nerve responses to sugars and artificial sweeteners (7, 40). Further, allelic variation in the Tas1r3 gene, which codes for the T1R3 protein (3,(17)(18)(19)24), contributes to strain differences in sensitivity (9), lick responsiveness (8, 10), peripheral taste nerve responsiveness (11), and daily intake and preference (11, 22) for sugars and artificial sweeteners.Sugars are not the only carbohydrates that have an attractive taste to some nonhuman species. Twenty years ago, our laboratory published a series of papers demonstrating that rats, mice, hamsters, and gerbils are strongly attracted to the taste of starch-derived glucose polymers such as Polycose and other maltodextrins (26). Behavioral and electrophysiological evidence indicates that Polycose and sucrose have qualitatively distinct taste sensations in rodents. For example, aversions conditioned to Polycose or sucrose do not cross-generalize, and some ta...