Glucose-induced taste preference memory requires NMDA and D1 signaling within the insular cortex.

The acquisition of taste preferences is critical for adaptive feeding, enabling animals to identify and prioritize nutrient-rich foods such as carbohydrates. This process relies on the integration of gustatory and post-ingestive signals, a function in which the insular cortex (IC) plays a key role. However, the neurochemical mechanisms within the IC that support glucose-induced taste preference memory remain poorly understood. Here, we examined neurotransmitter release in the IC during the acquisition of conditioned taste preference (CTP), an associative learning paradigm in which a neutral tastant is paired with a nutritive stimulus such as glucose. Our results demonstrate that a single i.p. administration of glucose (350 mg/kg) was sufficient to induce a robust, long-lasting CTP. Neurotransmitter monitoring revealed that saccharin consumption increased catecholamine release, whereas glucose administration elevated glutamate and dopamine levels in the IC. To determine the functional relevance of these signals, we locally infused antagonists of the NMDA (AP5), beta-adrenergic (propranolol), or D1-like dopaminergic receptors (SCH) into the IC 30 min after training. Behavioral testing showed that blockade of NMDA or dopamine D1 receptors selectively impaired long-term (72 h), but not short-term (4 h) memory, indicating a disruption of memory consolidation. Together, these findings identify glutamatergic and dopaminergic signaling in the IC, through NMDA and D1-like receptors activity, as critical substrates for the consolidation of glucose-induced CTP and offer novel mechanistic insight into how post-ingestive nutritive signals shape taste-guided behavior.