SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons

SCH-23390, a selective D-1 dopamine antagonist, was found to antagonize the locomotor stimulation induced by LY-171555, an action similar to that for haloperidol in control animals. However, this action of SCH-23390 was prevented in rats treated with 6-hydroxydopamine (6-OHDA) or with reserpine plus alpha-methyl-tyrosine pretreatment. These results indicate that the action of SCH-23390 to antagonize D-2 dopamine receptor actions is dependent upon functional catecholamine-containing neurons. In contrast to the lack of action of SCH-23390 to antagonize LY-171555 in 6-OHDA-treated rats, SCH-23390 blocked the locomotor stimulation induced by SKF-39393, a D-1 dopamine agonist, after this treatment. Thus, D-1 dopamine receptors are distinct from D-2 receptor sites and can exhibit a behavior similar to that observed when D-2 receptors are stimulated. These data suggest that D-1 receptor sites modulate D-2 dopamine receptor function through a mechanism dependent upon functionally intact catecholamine-containing neurons.