Critical role of NMDA but not opioid receptors in the acquisition of fat-conditioned flavor preferences in rats

Animals learn to prefer flavors associated with the intake of dietary fats such as corn oil (CO) solutions. We previously reported that fat-conditioned flavor preferences in rats were relatively unaffected by systemic treatment with dopamine D1 and D2 antagonsits. The present study examined whether systemic opioid (naltrexone, NTX) or NMDA (MK-801) receptor antagonists altered the acquisition and/or expression of CO-CFP. The CFP was produced by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in a 3.5% CO solution and another flavor (CS-, e.g., grape) in a 0.9% CO solution. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 d. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5 h after systemic administration of vehicle (VEH), NTX (0.1-5 mg/kg) or MK-801 (50-200 μg/kg). Rats displayed a robust CS+ preference following VEH treatment (85-88%) which was significantly though moderately attenuated by NTX (69-70%). The lower doses of MK-801 slightly reduced the CS+ preference; the high dose blocked the CS+ preference (49%) but also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH or NTX (0.1, 0.5, 1 mg/kg) or MK-801 (100 μg/kg) 0.5 h prior to 1-bottle training trials with CS+/3.5% CO and CS-/0.9% CO training solutions. Additional Limited VEH groups were trained with intakes limited to that of the NTX and MK-801 groups. Subsequent two-bottle CS+ vs. CS- tests were conducted without injections. Significant and persistent CS+ preferences were observed in VEH (77-84%) and Limited VEH (88%) groups. NTX treatment during training failed to block the acquisition of CO-CFP although the magnitude of the CS+ preference was reduced by 0.5 (70%) and 1.0 (72%) mg/kg doses relative to the Limited VEH treatment (88%). In contrast, MK-801 (100 μg/kg) treatment during training blocked the acquisition of the CO-CFP. These data suggest a critical role for NMDA, but not opioid receptor signaling in the acquisition of a fat conditioned flavor preferences, and at best limited involvement of NMDA and opioid receptors in the expression of a previously learned preference.