Prior exposure to nutritive and artificial sweeteners differentially alters the magnitude and persistence of sucrose-conditioned flavor preferences in BALB/c and C57BL/6 inbred mouse strains.

Murine genetic variance affects sucrose's ability to condition flavor preferences (CFP) relative to saccharin. Whereas BALB/c mice display robust sucrose- and fructose-CFP, C57BL/6 mice only display sucrose-CFP. Prior exposure to sucrose or saccharin solutions alters subsequent food choice responsiveness. The present study examined whether pre-exposure for one month to 10% sucrose or 0.2% saccharin altered subsequent sucrose-CFP in male and female BALB/c and C57BL/6 mice. Two weeks later, food-restricted mice were exposed to 10 CFP training trials with uniquely flavored 16% sucrose and 0.2% saccharin solutions. Two-bottle choice tests of the flavors mixed in saccharin followed for 4 weeks. Male mice weighed more than females across all conditions, and male BALB/c, but not C57BL mice consumed more 85 sucrose than females. No other notable sex differences were observed. BALB/c mice consumed more sucrose during pre-exposure and one-bottle training than C57BL/6 mice. Although the magnitudes of sucrose-CFP were comparable in two-bottle choice tests in water-exposed BALB/c and C57BL/6 mice, sucrose- and saccharin-exposed BALB/c mice displayed significantly greater sucrose-CFP preferences relative to C57BL/6 counterparts. These data indicate murine genetic variance in the effects of prior exposure to nutritive or non-nutritive sweeteners upon the magnitude of adult sugar-CFP.

Acquisition and expression of fat-conditioned flavor preferences are differentially affected by NMDA receptor antagonism in BALB/c and SWR mice.

Conditioned flavor preferences are elicited by fat (Intralipid) in inbred mouse strains with BALB/c and SWR mice displaying among the most robust preferences. Dopamine D1 and opioid receptor antagonism differentially reduces the acquisition (learning) and expression (maintenance) of fat-conditioned flavor preferences in these two strains. Because noncompetitive NMDA receptor antagonism with MK-801 differentially altered sugar-conditioned flavor preferences in these strains, and because NMDA receptors are involved in fat intake, the present study examined whether MK-801 differentially altered expression and acquisition of fat (Intralipid)-conditioned flavor preferences in BALB/c and SWR mice. In expression studies, food-restricted male mice alternately consumed a flavored (CS+, e.g., cherry, 5 sessions) 5% Intralipid solution and a differently-flavored (CS-, e.g., grape, 5 sessions) 0.5% Intralipid solution. Two-bottle CS choice tests occurred following vehicle or MK-801 (100, 200µg/kg). MK-801 blocked expression of Intralipid-CFP at both doses in BALB/c mice, but only at the 100µg/kg dose in SWR mice. In acquisition studies, groups of BALB/c (0, 100µg/kg) and SWR (0, 100µg/kg) male mice were treated prior to the ten acquisition training sessions followed by six 2-bottle CS choice tests without injections. MK-801 eliminated acquisition of Intralipid-conditioned flavor preferences in BALB/c mice, and actually changed the preference to an avoidance response in SWR mice. Thus, NMDA receptor signaling appears essential especially for the learning of fat-conditioned flavor preferences in both mouse strains.

NMDA receptor antagonism differentially reduces acquisition and expression of sucrose- and fructose-conditioned flavor preferences in BALB/c and SWR mice.

Conditioned flavor preferences (CFP) are elicited by sucrose and fructose relative to saccharin in rats and inbred mice. Whereas dopamine, but not opioid receptor antagonists interfere with the acquisition (learning) and expression (maintenance) of sugar-CFP in rats, these antagonists differentially affect acquisition and expression of sucrose- and fructose-CFP in BALB/c and SWR inbred mice. Given that NMDA receptor antagonism with MK-801 blocks acquisition, but not expression of fructose-CFP in rats, the present study examined whether MK-801 altered the expression and acquisition of sucrose- and fructose-CFP in BALB/c and SWR mice. In expression experiments, food-restricted mice alternately consumed a flavored (CS+, e.g., cherry, 5 sessions) 16% sucrose or 8% fructose+0.2% saccharin solution and a differently-flavored (CS-, e.g., grape, 5 sessions) 0.2% saccharin solution. 2-Bottle CS choice tests occurred following vehicle or MK-801 at doses of 100 or 200µg/kg. MK-801 mildly reduced the magnitude of the expression of sucrose- and fructose-CFP in BALB/c mice, and blocked the expression of fructose-, but not sucrose-CFP at the high dose in SWR mice. In acquisition experiments, groups of BALB/c (0, 100µg/kg) and SWR (0, 100, 200µg/kg) mice were treated prior to acquisition training sessions that was followed by 2-bottle CS choice tests without injections. MK-801 (100µg/kg) eliminated acquisition of sucrose- and fructose-CFP in BALB/c, but not SWR mice. The 200µg/kg MK-801 dose eliminated acquisition of sucrose- and fructose-CFP in SWR mice. Thus, NMDA receptor signaling is essential for the learning of both forms of sugar-CFP in both strains with BALB/c mice more sensitive to MK-801 dose effects.

BALB/c and SWR inbred mice differ in post-oral fructose appetition as revealed by sugar versus non-nutritive sweetener tests.

Recent studies indicate that C57BL/6J (B6) and FVB inbred mouse strains differ in post-oral fructose conditioning. This was demonstrated by their differential flavor conditioning response to intragastric fructose and their preference for fructose versus a non-nutritive sweetener. The present study extended this analysis to SWR and BALB/c inbred strains which are of interest because they both show robust flavor conditioning responses to fructose. In the first experiment, ad-libitum fed mice were given a series of 2-day, two-bottle preference tests between 8% fructose and a more preferred, but non-nutritive 0.1% sucralose +0.1% saccharin (S+S) solution (tests 1 & 4), and fructose or S+S versus water (tests 2 and 3). In test 1, SWR mice preferred S+S to fructose, and in tests 2 and 3, they preferred both sweeteners to water. In test 4, SWR mice switched their preference and consumed more fructose than S+S. In contrast, ad-libitum fed BALB/c mice strongly preferred S+S to fructose in both tests 1 and 4, although they preferred both sweeteners to water in tests 2 and 3. Food-restricted BALB/c mice also preferred the non-nutritive S+S to fructose in tests 1 and 4. The experience-induced fructose preference reversal observed in SWR, but not BALB/c mice indicates that fructose has a post-oral reinforcing effect in SWR mice as in FVB mice. Because B6 and FVB mice prefer glucose to fructose based on the post-oral actions of the two sugars, the second experiment compared the preferences of SWR and BALB/c mice for 8% glucose and fructose solutions. Ad-libitum fed and food-restricted SWR mice strongly preferred glucose to fructose. In contrast, ad-libitum fed BALB/c mice were indifferent to the sugars, perhaps because of their overall low intakes. Food-restricted BALB/c mice, however, strongly preferred glucose. These findings indicate that SWR and BALB/c mice differ in their preference response to the post-oral actions of fructose.