Roles of NMDA and dopamine D1 and D2 receptors in the acquisition and expression of flavor preferences conditioned by oral glucose in rats

•Conditioned flavor preferences (CFP) could be elicited by oral glucose consumption.•Dopamine D1 or D2 antagonists marginally attenuated oral glucose CFP expression.•NMDA antagonism marginally attenuated oral glucose CFP expression.•Dopamine D1 or D2 antagonists reduced oral glucose CFP acquisition.•NMDA antagonism reduced oral glucose CFP acquisition. Animals learn to prefer flavors associated with the intake of sugar (sucrose, fructose, glucose) and fat (corn oil: CO) solutions. Conditioned flavor preferences (CFP) have been elicited for sugars based on orosensory (flavor–flavor: e.g., fructose-CFP) and post-ingestive (flavor–nutrient: e.g., intragastric (IG) glucose-CFP) processes. Dopamine (DA) D1, DA D2 and NMDA receptor antagonism differentially eliminate the acquisition and expression of fructose-CFP and IG glucose-CFP. However, pharmacological analysis of fat (CO)-CFP, mediated by both flavor–flavor and flavor–nutrient processes, indicated that acquisition and expression of fat-CFP were minimally affected by systemic DA D1 and D2 antagonists, and were reduced by NMDA antagonism. Therefore, the present study examined whether systemic DA D1 (SCH23390), DA D2 (raclopride) or NMDA (MK-801) receptor antagonists altered acquisition and/or expression of CFP induced by oral glucose that should be mediated by both flavor–flavor and flavor–nutrient processes. Oral glucose-CFP was elicited following by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in 8% glucose and another flavor (CS−, e.g., grape) mixed in 2% glucose. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2h) over 10days. Subsequent two-bottle tests with the CS+ and CS− flavors mixed in 2% glucose occurred 0.5h after systemic administration of vehicle (VEH), SCH23390 (50–800nmol/kg), raclopride (50–800nmol/kg) or MK-801 (50–200μg/kg). Rats displayed a robust CS+ preference following VEH treatment (94–95%) which was significantly though marginally attenuated by SCH23390 (67–70%), raclopride (77%) or MK-801 (70%) at doses that also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH, SCH23390 (50–400nmol/kg), raclopride (50–400nmol/kg) or MK-801 (100μg/kg) 0.5h prior to ten 1-bottle training trials with CS+/8%G and CS−/2%G training solutions that was followed by six 2-bottle CS+ vs. CS− tests in 2% glucose conducted without injections. The significant and persistent CS+ preferences observed in the VEH (94