Dopamine D2 receptors mediate reversal learning in male C57BL/6J mice

Dopamine is critical for directing goal-oriented behavior. We investigated dopamine D₂ receptor involvement in reversal learning and reinforcement efficacy in mice lacking functional dopamine D₂ receptors and their heterozygous and wild-type littermates. Mice discriminated between two odors to receive a food reinforcer: One odor signaled a reinforcer (S⁺); the other odor signaled no reinforcer (S⁻). After mice learned the S⁺/S⁻ relationship, we inverted the reinforcement contingencies. The necessary number of trials to relearn the new reinforcement contingencies served as our index of reversal learning. Mice lacking functional dopamine D₂ receptors repeatedly failed to inhibit previously reinforced responses during reversal trials. In a separate experiment, mice responded for reinforcers on a progressive ratio schedule of reinforcement. Mice lacking functional dopamine D₂ receptors earned significantly fewer reinforcers than did heterozygous mice. Our results suggest that dopamine D₂ receptors regulate reversal learning and influence the reinforcing efficacy of natural rewards.