DIFFERENTIAL BEHAVIORAL INTERACTIONS BETWEEN THE DOPAMINE-D-1 ANTAGONIST SCH-23390 AND THE DOPAMINE-D-2 ANTAGONISTS METOCLOPRAMIDE AND SULPIRIDE IN NONHABITUATED MICE

This study investigated the effects of the selective D-1 antagonist SCH 23390, when administered alone and in combination with a typical (metoclopramide) or atypical neuroleptic (sulpiride), on species-typical behaviours in nonhabituated mice. When tested singly, all three compounds caused a progressive dose-dependent inhibition of locomotion, rearing and grooming, though their potencies varied widely. Mixtures of a threshold dose of 0.01 mg/kg SCH 23390 and metoclopramide (0.05-1.25 mg/kg) interacted synergistically to promote hypomotility and to decrease rearing, but did not affect grooming. By contrast, combinations of 0.01 mg/kg SCH 23390 and sulpiride (2-10 mg/kg) resulted in a marked potentiation of grooming, but only additive reductions in horizontal and vertical movements, consistent with sulpiride and metoclopramide occluding different populations of D-2 receptors. The results show that blockade of D-1 receptors and certain populations of D-2 receptors can interact positively to modify animal motor behaviour, and add a fresh perspective to the concept that these two types of dopamine receptor normally work interdependently to control movements of the body. © 1990.