THE DOPAMINE D-1, RECEPTOR ANTAGONIST SCH-23390 CAN EXERT D-1 AGONIST-LIKE EFFECTS ON RAT NUCLEUS-ACCUMBENS NEURONS

Interactions between the selective dopamine D-1-class receptor antagonist SCH 23390 and the dopamine D-2-class receptor agonist quinpirole on nucleus accumbens neurons were investigated with extracellular single cell recording and microiontophoresis. Because dopamine D-1 receptor stimulation enables many dopamine D-2 receptor-mediated effects, SCH 23390 was expected to antagonize quinpirole-induced inhibition of activity. Although concurrent iontophoretic administration of SCH 23390 attenuated the inhibitory effects of quinpirole on most neurons, the antagonist further suppressed the firing of most neurons during attempts to reverse quinpirole-induced inhibition. SCH 23390 also reinstated (enabled) quinpirole-induced inhibition in rats acutely depleted of dopamine. These findings suggest that under certain conditions, SCH 23390 may exert dopamine D-1 agonist-like effects.