Research ReportEffect of dopamine D1 and D2 receptor antagonism in the lateral hypothalamus on the expression and acquisition of fructose-conditioned flavor preference in rats

•Fructose-conditioned flavor preferences (CFP) are mediated by dopamine (DA).•Lateral hypothalamic (LH) DA D1 antagonism reduced fructose-CFP expression.•LH DA D2 antagonism failed to affect fructose-CFP expression.•Neither LH DA D1 nor D2 antagonism affected fructose-CFP acquisition.

The attraction to sugar-rich foods is influenced by conditioned flavor preferences (CFP) produced by the sweet taste of sugar (flavor-flavor learning) and the sugar's post-oral actions (flavor-nutrient) learning. Brain dopamine (DA) circuits are involved in both types of flavor learning, but to different degrees. This study investigated the role of DA receptors in the lateral hypothalamus (LH) on the flavor-flavor learning produced the sweet taste of fructose. In an acquisition study, food-restricted rats received bilateral LH injections of a DA D1 receptor antagonist (SCH23390), a D2 antagonist (RAC, raclopride) or vehicle prior to 1-bottle training sessions with a flavored 8% fructose+0.2% saccharin solution (CS+/F) and a less-preferred flavored 0.2% saccharin solution (CS−). Drug-free 2-bottle tests were then conducted with the CS+ and CS− flavors presented in saccharin. The fructose-CFP did not differ among groups given vehicle (76%), 12 nmol SCH (78%), 24 nmol (82%) or 24 nmol RAC (90%) during training. In an expression study with rats trained drug-free, LH injections of 12 or 24 nmol SCH or 12-48 nmol RAC prior to 2-bottle tests did not alter CS+ preferences (77-90%) relative to vehicle injection (86%). Only a 48 nmol SCH dose suppressed the CS+ preference (61%). The minimal effect of LH DA receptor antagonism upon fructose flavor-flavor conditioning differs with the ability of LH SCH injections to block the acquisition of glucose flavor-nutrient learning.