Dopamine D1 and D2 antagonists reduce the acquisition and expression of flavor-preferences conditioned by fructose in rats
Introduction
Animals use flavor cues (taste, odor, and texture) to guide their selection of nutritious foods and avoidance of toxic foods (Capaldi, 1996). Flavor-preferences and aversions, in turn, are based in part on learned associations between the various flavor elements in the foods, flavor–flavor conditioning, and between the flavor cues and postingestive consequences, flavor–nutrient, and flavor–toxin conditioning. A primary example of flavor–flavor conditioning is the acquired preference for an arbitrary flavor cue (e.g., banana extract) added to a sweet solution (e.g., saccharin solution; Holman, 1975). The naturally preferred sweet taste is considered to be an unconditioned stimulus (US) that reinforces the animal's preference for the added flavor, which represents the conditioned stimulus (CS).
The potent reward value of sweet taste may result, in part, because sweet taste activates mesolimbic dopamine (DA) circuits that are implicated in the mediation of natural as well as drug rewards. It has long been known that DA antagonists suppress the intake of sweet solutions in rats Geary and Smith, 1985, Muscat and Willner, 1989, Xenakis and Sclafani, 1981. Various findings suggest that this suppression results, in part, because DA antagonists reduce the reward value of sweet taste Schneider, 1989, Smith, 1995 although other explanations have been proposed to account for drug effects on food intake and reinforcement Berridge and Robinson, 1998, Ikemoto and Panksepp, 1999, Salamone et al., 1997. In addition to reducing the intake of sweet solutions, DA antagonists may also alter the ability of sweet solutions to reinforce the preference for other flavors. In particular, Hsiao and Smith (1995) reported that rats showed a reduced preference for a flavored 10% sucrose solution previously consumed while they were treated with the D2 antagonist raclopride compared to a differently flavored sucrose solution previously consumed while they were treated with saline.
Sucrose can reinforce flavor-preferences based on its sweet taste as well as its postingestive nutritive actions through the processes of flavor–flavor and flavor–nutrient conditioning, respectively (Sclafani, 1995). Hsiao and Smith (1995) used brief (5 min) training sessions to minimize postingestive factors, but the amount of sucrose consumed in the training sessions may have had a postingestive reinforcing action. To separate the effects of drugs on flavor–flavor and flavor–nutrient learning, our laboratories have used sham-feeding and intragastric (IG) infusion procedures, respectively Azzara et al., 2000, Azzara et al., 2001, Yu et al., 1999, Yu et al., 2000a, Yu et al., 2000b. With sham feeding, the ingested sucrose solution drains out of an open gastric fistula thereby minimizing postingestive nutrient actions (Weingarten and Watson, 1982). With the IG procedure, on the other hand, the sucrose is infused into the stomach thereby eliminating the sugar's taste as a conditioning factor (Sclafani, 1995). Yu et al., 2000a, Yu et al., 2000b used the sham-feeding procedure to determine the effects of DA antagonists on the acquisition and expression of flavor conditioning by the sweet taste of sucrose. Rats were treated with a D1 antagonist (SCH23390), a D2 antagonist (raclopride), or saline during sham-feeding training trials with different flavors added to a 16% sucrose solution or a less preferred 0.2% saccharin solution. In subsequent drug-free choice tests with both flavors presented in sucrose+saccharin solutions, the D1 and D2 groups displayed comparable preferences for the sucrose-paired flavor to those of saline-control rats that had their training intake limited to that of the drug groups, indicating a negligible effect on acquisition (Yu et al., 2000b). However, both antagonists dose-dependently reduced the preference for the CS+ flavor when administered prior to the choice test, indicating strong expression effects (Yu et al., 2000a).
The finding of Yu et al. (2000b) that DA antagonists did not block the acquisition of flavor conditioning by the sweet taste of sucrose would appear inconsistent with Hsiao and Smith's (1995) conditioning results as well as other studies suggesting that DA antagonists reduce the reward value of sweet taste (see Schneider, 1989, Smith, 1995). There are several procedural differences between the two conditioning studies that may account for the discrepant findings. In particular, Hsiao and Smith (1995) used a higher dose of raclopride and exposed their rats to less sucrose during training compared to the Yu et al. (2000b) study. In addition, the rats in the Hsiao and Smith (1995) study were given matched amounts of the raclopride-paired flavor and vehicle-paired flavor, whereas the drug-exposed rats in the Yu et al. (2000b) study were given unlimited access to the CS+ and CS− flavors, and both flavors were paired with raclopride.
In view of these considerations, the present study further investigated the effect of DA antagonism on flavor-preference learning produced by sweet taste. In this case, a conditioning procedure developed by Sclafani and Ackroff (1994) was used in which rats are trained to drink matched amounts of differently flavored 8% fructose and 0.2% saccharin solutions. This training procedure produces a robust preference for the fructose-paired flavor in a two-bottle choice test when both flavors are presented in 0.2% saccharin. Fructose, rather than sucrose or glucose, is used in this conditioning procedure because, unlike these other sugars, fructose has little or no postingestive reinforcing action during the short-term sessions. This is demonstrated by the failure of IG fructose infusions to condition a CS+ preference as well as by other findings Sclafani and Ackroff, 1994, Sclafani et al., 1993, Sclafani et al., 1999. Thus, the preference for a flavor that is mixed into a fructose solution is considered to be a form of flavor–flavor learning based on the more preferred taste of 8% fructose relative to 0.2% saccharin (Sclafani and Ackroff, 1994).
Section snippets
Experiment 1
The first experiment determined if treating rats with a D1 or D2 antagonist (200 nmol/kg SCH23390 or raclopride; Yu et al., 2000b) during one-bottle training with flavored fructose and saccharin solutions attenuated their learning of a preference for the fructose-paired flavor. In addition to a vehicle-treated control group, which was trained like the two drug groups, two additional vehicle-treated groups had their training intakes matched to those of the D1 and D2 groups, respectively. Drug
Experiment 2
Experiment 1 revealed that both SCH23390 and raclopride treatment during one-bottle training blocked the acquisition of a fructose-conditioned flavor-preference. The raclopride effect was particularly impressive because, contrary to expectations, the drug did not reduce the training intakes of the flavored fructose and saccharin solutions. Furthermore, the D2 rats, like vehicle-trained control rats, consumed significantly more fructose than saccharin during the initial 0.5 h of the training
General discussion
In confirmation of prior work (Sclafani and Ackroff, 1994), the control rats trained with flavored 8% fructose and 0.2% saccharin solutions displayed a significant (∼80%) preference for the fructose-paired flavor in choice tests with both flavors presented in saccharin solutions. This preference is attributed to the rats associating the CS+ flavor with the sweet taste of fructose rather than the sugar's postingestive actions. This assumption is based on findings showing that fructose has a
Acknowledgments
This research was supported in part by PSC/CUNY Grant 63278-00-32 (RJB). Mamta Shah (Stuyvesant High School) was supported by a New York Academy of Science High School Summer Research Program Fellowship.
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