Repeated administration of SCH 23390 enhances the SKF 38393-induced inhibition in the rat hippocampus

The functional modification of the D1 dopamine receptor subtype following acute or repeated administration of the D1 receptor antagonist SCH 23390 (0.5 mg/kg s.c.) was studied in the rat hippocampal slice preparation. The activity of the D1 receptor system was evaluated by measuring the effect of the D1 receptor agonist SKF 38393 on the spontaneous firing of CA1 hippocampal neurons. The testing was performed 1, 2 and 7 days after discontinuation of the treatment. Repeated (21 days, once daily), but not acute, administration of SCH 23390 significantly potentiated the inhibitory reaction to SKF 38393. The inhibition evoked by SKF 38393 was blocked by application of SCH 23390 (10(-8) M). The results show that repeated treatment with SCH 23390 enhances the inhibitory effect of SKF 38393 in the rat hippocampus, probably due to an increase in the number of D1 dopamine receptors.