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.
Ichihara
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Science, Meijo University, Nagoya, Japan.
Nabeshima
T
T
Kameyama
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects; D004873:Ergolines / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D019257:Quinpirole; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C043425:vanoxerine; D006220:Haloperidol