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

The study of inbred mouse strains is a useful animal model to assess differences in ingestive behavior responses, including conditioned flavor preferences (CFP). C57BL/6, BALB/c and SWR inbred mice display differential sensitivity to dopamine (DA) D1, opioid and muscarinic cholinergic receptor antagonism of sucrose or saccharin intake as well as to muscarinic cholinergic antagonism of acquisition (learning) of sucrose-CFP. Given that DA D1, opioid and N-methyl-D-aspartate (NMDA) receptor antagonists differentially alter sucrose-CFP in BALB/c and SWR inbred mice, the present study examined whether systemic administration of naltrexone, SCH23390 or MK-801 altered acquisition and expression of sucrose-CFP in C57BL/6 mice. In acquisition experiments, male food-restricted C57BL/6 mice were treated with vehicle, naltrexone (1, 5 mg/kg), SCH23390 (50, 200 nmol/kg) or MK-801 (100, 200 µg/kg) 30 min prior to each of ten daily sessions in which they alternately consumed a flavored (CS+, e.g. cherry) 16% sucrose solution and a differently-flavored (CS-, e.g. grape) 0.05% saccharin solution followed by six two-bottle CS choice tests mixed in 0.2% saccharin without injections. SCH23390 and MK-801, but not naltrexone eliminated sucrose-CFP acquisition in food-restricted C57BL/6 mice. In expression experiments, food-restricted C57BL/6 mice underwent the ten 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). SCH23390 more effectively reduced the magnitude of sucrose-CFP expression than naltrexone or MK-801 in food-restricted C57BL/6 mice. Thus, dopamine D1 and NMDA receptor signaling is essential for learning of sucrose-CFP in C57BL/6 mice.

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.

Murine genetic variance in muscarinic cholinergic receptor antagonism of acquisition and expression of sucrose-conditioned flavor preferences in three inbred mouse strains.

Conditioned flavor preferences (CFP) are elicited by sucrose relative to saccharin in inbred mice with both the robustness of the preferences and sensitivity to pharmacological receptor antagonists sensitive to genetic variance. Dopamine, opioid and N-methyl-d-aspartate receptor antagonists differentially interfere with the acquisition (learning) and expression (maintenance) of sucrose-CFP in BALB/c and SWR inbred mice. Further, the muscarinic cholinergic receptor antagonist, scopolamine (SCOP) more potently reduces both sucrose and saccharin intake in BALB/c and C57BL/6 relative to SWR inbred mice. The present study examined whether SCOP altered the expression and acquisition of sucrose-CFP in BALB/c, C57BL/6 and SWR mice. In expression experiments, food-restricted mice alternately consumed a flavored (CS+, e.g., cherry, 5 sessions) 16% sucrose solution and a differently-flavored (CS-, e.g., grape, 5 sessions) 0.05% saccharin solution. Two-bottle CS choice tests with the two flavors mixed in 0.2% saccharin solutions occurred following vehicle or SCOP at doses of 1 or 5 mg/kg. SCOP significantly reduced the magnitude of the expression of sucrose-CFP in BALB/c, but not either C57BL/6 or SWR mice. In acquisition experiments, separate groups of BALB/c, C57BL/6 and SWR mice were treated prior to acquisition training sessions with vehicle or 2.5 or 5 mg/kg SCOP doses that was followed by six two-bottle CS choice tests without injections. SCOP dose-dependently reduced (1 mg/kg) and eliminated (2.5 mg/kg) the acquisition of sucrose-CFP in BALB/c mice, and reduced the magnitude of acquisition of sucrose-CFP in SWR mice. In contrast, neither SCOP dose affected the acquisition of sucrose-CFP in C57BL/6 mice. Thus, muscarinic cholinergic receptor signaling is essential for the learning of sucrose-CFP in BALB/c mice, to a lesser degree in SWR mice, but not in C57BL/6 mice. Murine genetic variance differentially modulates muscarinic cholinergic receptor control of sweet intake per se relative to learned conditioned flavor preferences of sweets.

Murine genetic variance in muscarinic cholinergic receptor antagonism of sucrose and saccharin solution intakes in three inbred mouse strains.

Nutritive (e.g., sucrose) and non-nutritive (e.g., saccharin) sweeteners stimulate intake in inbred mouse strains. BALB/c, SWR and C57BL/6 mice differ in the ability of dopamine (DA) D1 (SCH23390) and opioid (naltrexone) receptor antagonism to alter sucrose intake. Whereas SCH23390 comparably reduced cumulative sucrose intake in all three strains, naltrexone reduced cumulative sucrose intake maximally in C57/BL/6 mice, in intermediate fashion in BALB/c mice, but not in SWR mice. Whereas cumulative saccharin intake was reduced by DA D1 receptor antagonism in BALB/c and SWR mice, naltrexone was more potent in SWR relative to BALB/c mice. The present study first examined whether SCH23390 (50-1600nmol/kg) and naltrexone (0.01-5mg/kg) altered saccharin intake in C57BL/6 mice. Given that scopolamine (SCOP), a muscarinic cholinergic receptor antagonist, reduces sweet intake in outbred rats, a second experiment examined whether SCOP (0.1-10mg/kg) altered 0.2% saccharin and 10% sucrose intakes in BALB/c, SWR and C57BL/6 mice. Cumulative saccharin intake was significantly reduced by SCH23390 (200-1600nmol/kg; ID40=175nmol/kg) and naltrexone (0.1-5mg/kg; ID40>5mg/kg) in C57BL/6 mice. Cumulative sucrose intake was significantly reduced following SCOP in C57BL/6 (0.1-10mg/kg; ID40=2.32mg/kg) and BALB/c (2.5-10mg/kg; ID40=0.52mg/kg) mice. In contrast, SWR mice (ID40=41.61mg/kg) only displayed transient (15min) reductions in sucrose intake following SCOP (2.5-10mg/kg). Cumulative saccharin intake was significantly reduced following SCOP in C57BL/6 and BALB/c mice (0.1-10mg/kg; ID40<0.1mg/kg). In contrast, SWR mice (ID40=2.28mg/kg) displayed smaller significant reductions in saccharin intake following SCOP (0.1-10mg/kg). These data indicate that although both nutritive and non-nutritive sweet intakes are governed by muscarinic cholinergic receptor signaling, this process is subject to murine genetic variance with greater sensitivity observed in C57BL/6 and BALB/c relative to SWR inbred mouse strains.