Flavor preference conditioning by different sugars in sweet ageusic Trpm5 knockout mice

- Trpm5 knockout (KO) mice have a greatly impaired sweet taste.
- KO mice learn to prefer sugar-paired flavors based on post-oral nutritive effects.
- They show strong preferences for glucose and galactose, but not fructose flavors.
- They also prefer a flavor paired with a non-metabolizable glucose analog.

Knockout (KO) mice missing the taste signaling protein Trpm5 have greatly attenuated sweetener preferences but develop strong preferences for glucose in 24-h tests, which is attributed to post-oral sugar conditioning. Trpm5 KO mice express mild preferences for galactose but no preferences for fructose in 24-h tests, which suggests that these sugars differ in their post-oral reinforcing effects. Here we investigated sugar-conditioned flavor preferences in Trpm5 KO and C57BL/6J wildtype (B6) mice. The mice were trained to consume a flavored (CS+, e.g. grape) 8% sugar solution and flavored (CS−, e.g., cherry) water on alternating days followed by two-bottle choice tests with CS+ vs. CS− flavors in water and with unflavored sugar vs. water. The KO mice displayed strong preferences (> 80%) for the CS+ glucose and CS+ galactose but not for the CS + fructose flavor. They also preferred glucose and galactose, but not fructose to water. In contrast, the B6 mice preferred all three CS + flavors to the CS− flavor, and all three sugars to water. In tests with the non-metabolizable sugar α-methyl-d-glucopyranoside (MDG), the KO and B6 mice preferred 8% MDG to water but did not prefer the CS+ 8% MDG to CS−. However, they preferred a CS + flavor mixed with 4% MDG over the CS− flavor. Trpm5 KO mice also preferred galactose and MDG to fructose in direct choice tests. The Trpm5 KO data indicate that glucose and, to a lesser extent, galactose and MDG have post-oral reinforcing actions that stimulate intake and preference while fructose has a much weaker effect. The CS+ flavor and sugar preferences of B6 mice may be mediated by the sweet taste and/or post-oral actions of the various sugars. Glucose, galactose, and MDG, but not fructose, are ligands for the sodium-glucose transporter 1 (SGLT1) which is implicated in post-oral sugar conditioning in B6 mice.