Acquisition and expression of fat conditioned flavor preferences following dopamine D1, opioid and NMDA receptor antagonism in C57BL/6 mice.

Objectives: Inbred mouse strains differ in the pharmacology mediating sugar and fat intake and conditioned flavor preferences (CFP). C57BL/6, BALB/c and SWR inbred mice are differentially sensitive to dopamine (DA) D1, opioid and muscarinic receptor antagonism of sucrose, saccharin or fat intake, and to DA, opioid, muscarinic and N-methyl-D-aspartate (NMDA) receptor antagonism of acquisition of sucrose-CFP. DA D1, opioid and NMDA receptor antagonists differentially alter fat (Intralipid)-CFP in BALB/c and SWR mice. The present study examined whether naltrexone, SCH23390 or MK-801 altered acquisition and expression of Intralipid-CFP in C57BL/6 mice.Methods: In acquisition, groups of male food-restricted C57BL/6 mice received vehicle, naltrexone (1, 5 mg/kg), SCH23390 (50, 200 nmol/kg) or MK-801 (100, 200 µg/kg) before 10 training sessions in which mice alternately consumed two novel-flavored 5% (CS+) and 0.5% (CS-) Intralipid solutions. Six two-bottle CS choice tests followed with both flavors mixed in 0.5% Intralipid without injections. In expression, C57BL/6 mice underwent the 10 training sessions without injections followed by two-bottle CS choice tests 30 min following vehicle, naltrexone (1, 5 mg/kg), SCH23390 (200, 800 nmol/kg) or MK-801 (100, 200 µg/kg).Results: Fat-CFP acquisition in C57BL/6 mice was significantly though marginally reduced following naltrexone, SCH23390 and MK-801. Fat-CFP expression was similarly reduced by naltrexone, SCH23390 and MK-801 in C57BL/6 mice. Discussion: C57BL/6 mice were more sensitive to DA D1, opioid and NMDA antagonists in the expression of fat-CFP relative to sugar-CFP, but were less sensitive to DA D1 and NMDA antagonists in the acquisition of fat-CFP relative to sugar-CFP.

Strain differences in muscarinic cholinergic receptor antagonism of fat intake and acquisition and expression of fat-conditioned flavor preferences in male BALB/c, C57BL/6 and SWR mice.

Murine strain differences occur for both intakes of and preferences for sugars and fats. Previous studies demonstrated that the muscarinic cholinergic receptor antagonist, scopolamine (SCOP) more potently reduced sucrose and saccharin intakes in inbred C57BL/6 and BALB/c than SWR mice, sucrose-conditioned flavor preferences (CFP) expression in BALB/c, but not C57BL/6 or SWR mice, and sucrose-CFP acquisition in BALB/c relative to SWR and C57BL/6 mice. Although fat intake and fat-CFP are observed in all three strains, strain-specific effects were previously observed following dopamine D1, opiate and NMDA receptor antagonism of sweet and fat intake and CFP. The present study investigated whether muscarinic receptor antagonism differentially affected fat (Intralipid) intake and preferences in these strains by examining whether SCOP altered fat (Intralipid) intake and fat-CFP expression and acquisition in BALB/c, C57BL/6 and SWR mice. SCOP (0.1-10 mg/kg) significantly reduced Intralipid (5%) intake in all three strains across 2 h. In fat-CFP expression experiments, food-restricted mice consumed one flavored (conditioned stimulus (CS)+, 5 sessions) Intralipid (5%) solution and a differently-flavored (CS-, 5 sessions) Intralipid (0.5%) solution. Two-bottle CS choice tests with the two flavors mixed in 0.5% Intralipid occurred following vehicle and two SCOP doses (1, 5 mg/kg). SCOP elicited small, but significant reductions in fat-CFP expression in BALB/c and C57BL/6, but not SWR mice. In fat-CFP acquisition experiments, separate groups of BALB/c, C57BL/6 and SWR mice were treated prior to the ten acquisition training sessions with vehicle or two SCOP (2.5, 5 mg/kg) doses followed by six two-bottle choice tests without injections. SCOP eliminated fat-CFP acquisition in all three strains. Thus, muscarinic receptor signaling mediates learning, and to a lesser degree maintenance of fat-CFP while maximally inhibiting fat intake in the three strains.