Opposing roles of D1 and D2 receptors in appetitive conditioning

Abstract

Previous studies have shown that D(1) receptor blockade disrupts and D(2) receptor blockade enhances long-term potentiation. These data lead to the prediction that D(1) antagonists will attenuate and D(2) antagonists will potentiate at least some types of learning. The prediction is difficult to test, however, because disruptions in either D(1) or D(2) 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 D(1) antagonist SCH23390 (0, 0.4, 0.8, and 0.16 mg/kg) or D(2) antagonist 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, D(1) and D(2) family receptor antagonists disrupt and promote learning, respectively, as predicted by the effects of D(1) and D(2) receptor blockade on neuronal plasticity.

Fig. 1.

Latency to enter the food compartment during food presentation during 17 d of magazine training.

Fig. 2.

Head entries during the 10 sec before CS onset, the 6 sec CS, and the 16 sec after CS offset. Food was delivered 3 sec after CS onset. The figure shows head entries for three representative rats, one in the vehicle group (top), one in SCH at 0.16 mg/kg (middle), and one in raclopride at 0.4 mg/kg (bottom). Horizontal bars indicate the presence of the rat's head in the food compartment during each of the 28 conditioning trials (with successive trials represented frombottom to top). Note the normal latencies to respond to food presentation in SCH- and RAC-treated rats.

Fig. 3.

Both SCH23390 and raclopride reduced locomotor activity on tone conditioning–drug treatment day

Fig. 4.

Performance of each treatment group during day 19, the drug-free test session. The y-axis shows mean proportion of trials during which rats' heads were in the food compartment for each successive 100 msec bin during the 10 sec before tone onset (−10 to 0), the presentation of the tone (0–6), and the 10 sec after tone offset (6–16). As can be seen, rats that had received UNPAIRED presentations of CS and food showed reduced CS period head-in durations compared with paired CS–food controls. Animal that were under the influence of the highest SCH23390 dose during tone–food pairings also showed a reduced CS head-in probability. Animals that were under the influence of RAC during the tone–food pairings showed increased CS head-in probabilities compared with vehicle controls on test day.