Sugar appetite is influenced by unlearned attractions to sweet taste and learned responses to sugars’ taste and post-ingestive actions. In rats, sugar-conditioned flavor preferences (CFP) are attenuated by dopamine D1 (SCH23390: SCH), but not opioid (naltrexone: NTX), receptor antagonism. Sucrose-CFP occurs in BALB/c and SWR inbred mice that differ in their suppressive effects of SCH and NTX on sucrose intake. The present study examined whether SCH and NTX altered expression of a previously learned sucrose-CFP and acquisition (learning) of sucrose-CFP in these strains. In Experiment 1, food-restricted mice were trained (10 one-bottle sessions) to drink a more-preferred flavored (e.g., cherry) 16% sucrose solution (CS+/Sucrose) on odd-numbered days, and a less-preferred flavored (e.g., grape) 0.05% saccharin solution (CS−/Saccharin) on even-numbered days. Two-bottle tests with the flavors mixed in 0.2% saccharin occurred 30 min following vehicle (Veh), SCH (50–800 nmol/kg) or NTX (1–5 mg/kg) assessing preference expression. CS+ preference expression in BALB/c and SWR mice following Veh were significantly reduced by SCH and NTX. In Experiment 2, separate groups of BALB/c and SWR mice received Veh, SCH (50 nmol/kg) or NTX (1 mg/kg) injections 30 min prior to daily one-bottle training sessions with the CS+/Sucrose and CS−/Saccharin solutions assessing preference acquisition. Subsequent two-bottle tests with the CS+ vs. CS− solutions were conducted without injections. CS+/Sucrose training intakes were reduced by SCH in both strains and by NTX in BALB/c mice. In the initial two-bottle test, sucrose-CFP acquisition was significantly reduced in BALB NTX (54%), but not in BALB SCH (77%) groups relative to the BALB Veh group (85%). In contrast, sucrose-CFP acquisition was significantly reduced in SWR SCH (61%), but not in SWR NTX (83%) groups relative to the SWR Veh group (86%). DA D1 and opioid receptor signaling modulate acquisition and/or expression of sucrose-CFP in mice with significant strain differences observed.

Preference for and intake of solid and emulsified fat (Intralipid) solutions vary across different mouse strains. Fat intake in rodents is inhibited by dopamine and opioid receptor antagonists, but any variation in these responses as a function of genetic background is unknown. Therefore, the present study compared the ability of dopamine D1-like (SCH23390) and general opioid (naltrexone) receptor antagonism to alter intake of fat emulsions (Intralipid) in mice. Two-h intakes of 5% Intralipid were measured (5-120 min) in seven inbred (BALB/c, C57BL/6, C57BL/10, DBA/2, SJL, SWR, 129P3) and one outbred (CD-1) mouse strains following treatment with vehicle, SCH23390 (50-1600 nmol/kg, ip) and naltrexone (0.001-5 mg/kg, sc). SCH23390 significantly, dosedependently and differentially reduced Intralipid intake at all five (DBA/2, SWR, CD-1), four (SJL, C57BL/6), three (129P3) and one (C57BL/10) of the doses tested, but failed to affect Intralipid intake in BALB/c mice. Naltrexone significantly, dose-dependently and differentially reduced Intralipid intake at all four (DBA/2), three (SWR, SJL), two (CD-1, C57BL/10) and one (C57BL/6, 129P3) of the doses tested, and also failed to affect Intralipid intake in BALB/cJ mice. SCH23390 and naltrexone were respectively 13.3-fold and 9.3-fold more potent in inhibiting Intralipid intake in the most sensitive (DBA/2) relative to the least sensitive (BALB/c) mouse strains. A strong positive relationship (r=0.91) was observed for the abilities of SCH23390 and naltrexone to inhibit Intralipid intake across strains. These findings indicate that dopaminergic and opioid signaling mechanisms differentially control Intralipid intake across different mouse strains, suggesting important genetic and pharmacological interactions in the short-term control of rewarding and post-ingestive consequences of fat intake.

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 days. 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 ug/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 ug/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 ug/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.