Dissociation between amiloride-sensitive taste responses and ingestive behavior to sodium ascorbate in osteogenic disorder Shionogi rats

Abstract Sodium ascorbate (AsA-Na) is widely used as a source of vitamin C. However, the mechanisms regulating voluntary intake across different concentrations and nutritional states remain poorly understood. Therefore, we examined behavioral and neural responses to AsA-Na in osteogenic disorder Shionogi (ODS) od/od rats, which lack endogenous vitamin C synthesis. Two-bottle choice tests were used to evaluate long-term behavioral responses and the contribution of epithelial sodium channel (ENaC)-dependent taste signaling was examined using amiloride. In parallel, chorda tympani (CT) nerve responses were recorded with and without amiloride treatment. AsA-Na consistently showed lower preference scores than NaCl across concentrations. At 30–100 mM, the preference for AsA-Na was lower than that for NaCl but significantly higher than that for AsA. Lick responses to AsA-Na were comparable to those for NaCl and were enhanced under vitamin C-deficient conditions. Although the 48-h intake of 100 mM AsA-Na remained low under all conditions, the intake of 10 mM AsA-Na increased selectively during the re-intake phase. Notably, amiloride strongly suppressed CT nerve responses to AsA-Na. While amiloride significantly reduced NaCl preference and intake, it had no effect on AsA-Na preference or sustained intake. These results support a dissociation between ENaC-mediated peripheral sensory signaling and long-term ingestive behavior. Although AsA-Na is detected via sodium taste pathways, this sensory input alone cannot account for sustained intake. Instead, intake is likely influenced by post-ingestive mechanisms in a concentration- and state-dependent manner. These findings suggest an important contribution of internal nutritional signals in shaping chemosensory-driven behavior.