Mediation of dopamine D₁ and D₂ receptors in the effects of GBR 12909 on latent learning and locomotor activity in mice

We investigated the involvement of dopamine D₁ and D₂ receptor subtypes in the effects of GBR 12909, a selective dopamine uptake inhibitor, on latent learning in the performance of a water-finding task and on locomotor activity in mice. GBR 12909 (10 and 20 mg/kg) impaired latent learning, and this effect was counteracted by the dopamine D₂ receptor antagonist, (-)-sulpiride (20 and 40 mg/kg), but not by the dopamine D₁ receptor antagonist, SCH 23390 (0.025 and 0.05 mg/kg). The dopamine D₂ receptor agonist, quinpirole (0.5 and 1 mg/kg) and the dopamine D₁ receptor agonist, SKF 38393 (20 mg/kg) impaired latent learning, but both effects were less than that of GBR-12909. The effect of quinpirole, but not of GBR 12909, on latent learning was potentiated by combination with SKF 38393. In contrast to its effect on learning, SCH 23390 (0.025 and 0.05 mg.kg) was more effective to suppress the stimulant effect of GBR 12909 on locomotor activity than was (-)-sulpiride (40 and 80 mg/kg). These findings suggest that both dopamine D₁ and D₂ receptors play an important role in the action of endogenously released dopamine in latent learning and locomotor activity, and that while the dopamine D₂ receptor is involved predominantly in latent learning, both dopamine D₁ and D₂ receptors play a critical role in locomotor activity.