Role of glutamatergic signaling in the acquisition and expression of learned sugar preferences in C57BL/6 mice.

C57BL/6 (B6) mice learn to prefer glucose or sucrose to initially isopreferred or even more preferred nonnutritive sweeteners due to the postoral appetite stimulating (appetition) actions of glucose. Recent evidence indicates that specific duodenal neuropod cells transmit the glucose appetition signal to the brain via glutamatergic synaptic connections with vagal afferents. The present study found that intraperitoneal pretreatment with a glutamatergic receptor antagonist cocktail (kynurenic acid (KA)/D-2-amino-3-phosphonopentanoic acid (AP3)) in B6 mice did not block the expression of their learned preference for 8% glucose solution over an initially-preferred 0.1% sucralose + 0.1% saccharin solution. However, acquisition of the glucose preference was blocked by drug treatment during 1-h training sessions with the two sweeteners. Systemic KA/AP3 injections also did not block the expression of the learned preference for a 10.6% sucrose solution over a 0.6% sucralose solution. Drug effects on the acquisition of the sucrose preference were not determined because sucrose, unlike glucose conditioning, required 24-h training trials. The findings that the 1-h training regimen conditioned 8% glucose, but not 10.6% sucrose, preferences suggest that glucose has more potent appetition actions. This was confirmed by the finding that B6 mice learned to prefer 10.6% glucose to 10.6% sucrose after 1-h or 24-h training despite an initial strong sucrose preference. This action can be explained by 10.6% sucrose's digestion in the gut to glucose and fructose with only glucose activating the gut-brain appetition pathway.