Opposing Roles of D1 and D2 Receptors in Appetitive Conditioning

Previous studies have shown that D1receptor blockade disrupts and D2 receptor blockade enhances long-term potentiation. These data lead to the prediction that D1 antagonists will attenuate and D2 antagonists will potentiate at least some types of learning. The prediction is difficult to test, however, because disruptions in either D1 or D2 transmission lead to reduced locomotion, exploration, and response execution and are therefore likely to impair learning that requires behavioral responding (including exploration of an environment) during the learning episode. Under a paradigm that minimizes motor requirements, rats were trained to enter a food compartment during pellet presentation. Animals then received tone–food pairings under the influence of D1antagonist SCH23390 (0, 0.4, 0.8, and 0.16 mg/kg) or D2antagonist raclopride (0, 0.2, 0.4, and 0.8 mg/kg). An additional group received unpaired presentations of tone and food. On a drug-free test day 24 hr later, animals that had been under the influence of SCH23390 (like animals that had received unpaired presentations of tone and food) showed reduced head entries in response to the tone, whereas animals that had been under the influence of raclopride showed increased head entries in response to the tone compared with vehicle controls. These data demonstrate that, under a conditioned approach paradigm, D1 and D2 family receptor antagonists disrupt and promote learning, respectively, as predicted by the effects of D1 and D2 receptor blockade on neuronal plasticity.