Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats

Abstract

Systemic administration of dopamine D1 (SCH23390) and less so D2 (raclopride) receptor antagonists significantly reduce acquisition and expression of fructose-conditioned flavor preferences (CFP). Because dopamine in the nucleus accumbens shell (NAcS) is implicated in food reward, the present study examined whether NAcS D1 or D2 antagonists altered acquisition and/or expression of fructose-CFP. In Experiment 1, food-restricted rats with bilateral NAcS cannulae were trained to drink a fructose (8%)+saccharin (0.2%) solution mixed with one flavor (CS+/Fs) and a less-preferred 0.2% saccharin solution with mixed another flavor (CS-/s). Unlimited two-bottle tests with the two flavors in saccharin (0.2%: CS+/s, CS-/s) occurred 10 min following total bilateral NAcS doses of 0, 12, 24 or 48 nmol of SCH23390 or raclopride. Preference for CS+/s over CS-/s following vehicle treatment (76%) was significantly reduced by SCH23390 (48 nmol, 62%) and raclopride (24 nmol, 63%). In Experiment 2, rats received bilateral NAcS injections (12 nmol) of SCH23390 or raclopride on one-bottle training (16 ml) days. Yoked control rats received vehicle and were limited to the CS intakes of the D1 and D2 groups, whereas untreated controls without injections received their CS ration during training. Subsequent unlimited two-bottle tests revealed initial preferences of CS+/s over CS-/s in all groups that remained stable in untreated and yoked controls, but were lost over the six tests sessions in D1 and D2 groups. These data indicate that NAcS D1 and D2 antagonists significantly attenuated the expression of the fructose-CFP and did not block acquisition, but hastened extinction of fructose-CFP.

Figure 1

Bilateral representation of cannula sites aimed at the nucleus accumbens shell (NAcS) region of 56 rats using Figures 12, 13 and 14 of the stereotaxic atlas of Paxinos and Watson [22]. The bilateral cannulae were localized within the shell region of the NAcS, or bordered the core and shell regions of the NAc, or bordered the NAcS and immediately adjacent ventral diagonal band area. Multiple animals had highly similar cannula placements, and there was considerable overlap of placements for the animals receiving SCH23390 (SE, n=12) and raclopride (RE, n=12) in the Expression paradigm, and for the animals receiving SCH23390 (SA, n=7), raclopride (RA, n=6) and vehicle (Yoked Control, YA, n=19) in the Acquisition paradigm.

Figure 2. (Exp 1. Expression Procedure)

Intakes (mean ±SEM, 0.5 h) of CS+/s and CS−/s solutions in two-bottle tests in animals receiving bilateral NAcS injections of the D1 dopamine antagonist, SCH23390 (upper panel) or the D2 dopamine antagonist, raclopride (lower panel) at total doses of 0, 12, 24 or 48 nmol 10 min prior to testing. Significant differences are denoted between CS+/s and CS−/s intake within an injection condition (*) and between CS+/s intake following a drug dose relative to the vehicle treatment (+). The percentages of CS+/s intake over total intake are denoted above each pair of values with significant differences relative to vehicle treatment (#) noted.

Figure 3. (Acquisition Study)

Intakes (mean ±SEM, 1 h) of three pairs of CS+/s and CS−/s solutions during three pairs of two-bottle tests. During training, the D1 group received NAcS injections of SCH23390 (12 nmol, Panel A) and the D2 group received NAcS injections of raclopride (12 nmol, Panel B); the Yoked Control group received NAcS vehicle injections (Panel C) while the Control group (Panel D) received no injections during training. Significant differences are denoted between CS+/s and CS−/s intake within each test are denoted (*) as are significant differences in the percentage of CS+/s intake over total intake (#).