Behavioral economics of food reinforcement and the effects of prefeeding, extinction, and eticlopride in dopamine D₂ receptor mutant mice

Rationale Several studies have investigated the reinforcing effects of food in genetically engineered mice lacking dopamine D₂ receptors (DA D₂Rs); however, behavioral economic analyses quantifying reinforcement have not been conducted. Objective The role of DA D₂Rs in food reinforcement was examined by comparing responding under various fixedratio (FR) schedules of reinforcement, and effects of extinction, satiation, and the DA D₂R antagonist eticlopride, in mice with and without genetic deletions of the receptor. Results Response rates of DA D ₂R knockout (KO) mice were generally lower than those of littermate wild-type (WT) and heterozygous (HET) mice. The demand curve (consumption vs. FR value) for KO mice decreased more steeply than that of HET or WT mice, suggesting that reinforcing effectiveness is decreased with DA D₂R deletion. Prefeeding decreased, whereas extinction increased overall response rates as a proportion of baseline, with no significant genotype differences. Both (+)- and (-)-eticlopride dose-dependently decreased responding in all genotypes with (-)-eticlopride more potent than (+)-eticlopride in all but KO mice. The enantiomers were equipotent in KO mice, and similar in potency to (+)-eticlopride in WT and HET mice. Conclusions That prefeeding and extinction did not vary across genotypes indicates a lack of involvement of DA D ₂Rs in these processes. Differences between (-)-eticlopride effects and extinction indicate that DA D₂R blockade does not mimic extinction. The maintenance of responding in KO mice indicates that the DA D₂R is not necessary for reinforcement. However, the economic analysis indicates that the DA D₂R contributes substantially to the effectiveness of food reinforcement.