👤 Anthony Sclafani

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 by 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 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 (1-5mg/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 (1mg/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. Show less

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-hour 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, dose-dependently 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. Show less

Rats learn to prefer flavors paired with the post-oral effects of glucose. The present study examined how rapidly they acquire this preference. In Experiment 1, food-restricted rats were given repeated three-session training/testing cycles: one 30-min session with a CS+ flavor paired with intragastric (IG) infusion of 16% glucose, another session with a CS- flavor paired with IG water, and a third session with a choice between the flavors with their infusates. The rats preferred the CS+ (69%) in the first choice session, and preference increased across the six cycles to 86%. These data demonstrate that the post-oral reinforcing action of glucose is potent enough to support one-trial learning. In Experiment 2, two groups of rats were trained in the same way, with the CS+ flavor paired with IG infusion of 16% glucose or 7.1% corn oil emulsion, but tests were conducted under extinction conditions, with both CS+ and CS- flavors paired with IG water. Significant preference for the CS+ was acquired more rapidly with glucose (71% CS+ in test 1) than with oil (69% CS+ in test 4). Consistent with previous work, the post-oral stimulation by glucose was more potent than that of isocaloric oil emulsion in conditioning preferences. The last experiment examined the acquisition rate for a flavor-taste conditioned preference. Rats were trained with a CS+ flavor mixed into an 8% fructose + 0.2% saccharin solution and a CS- flavor in 0.2% saccharin. The same three-session training/testing cycles were used, and in the tests the flavors were presented in saccharin. A significant 74% preference for the CS+ flavor was apparent by the second test. Together these studies show that the acquisition of flavor preferences, whether based on flavor-taste or flavor-nutrient associations, can be quite rapid. Show less

Preference and intake of sucrose varies across inbred and outbred strains of mice. Pharmacological analyses revealed that the greatest sensitivity to naltrexone-induced inhibition of sucrose (10%) intake was observed in C57BL10/J and C57BL/6J strains, whereas 129P3/J, SWR/J and SJL/J strains displayed far less sensitivity to naltrexone-induced inhibition of sucrose intake. Given that dopamine D1 (SCH23390) and D2 (raclopride) receptor antagonism potently reduce sucrose intake in outbred rat and mouse strains, the present study examined the possibility of genetic variance in the dose-dependent (50-1600 nmol/kg) and time-dependent (5-120 min) effects of these antagonists upon sucrose (10%) intake in the eight inbred (BALB/cJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J, SWR/J and 129P3/J) and one outbred (CD-1) mouse strains previously tested with naltrexone. SCH23390 significantly reduced sucrose intake across all five doses in 129P3/J and SJL/J mice, across four doses in C57BL/6J and BALB/cJ mice, across three doses in DBA/2J, SWR/J, C3H/HeJ and C57BL/10J mice, but only at the two highest doses in CD-1 mice. SCH23390 was 2-3-fold more potent in inhibiting sucrose intake in 129P3/J and SJL/J mice relative to CD-1 mice. In contrast, only the highest equimolar 1600 nmol/kg dose of raclopride significantly reduced sucrose intake in the BALB/cJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J and 129P3/J, but not the SWR/J and CD-1 strains. The present and previous data demonstrate specific and differential patterns of genetic variability in inhibition of sucrose intake by dopamine and opioid antagonists, suggesting that distinct neurochemical mechanisms control sucrose intake across different mouse strains. Show less