Effects of daily SKF 38393, quinpirole, and SCH 23390 treatments on locomotor activity and subsequent sensitivity to apomorphine

Abstract

In three experiments, male Wistar rats (250-350 g) were injected (SC) daily with the D1-type dopamine receptor agonist, SKF 38393 (0.0, 4.0, 8.0, or 16.0 mg/kg), the D2-type dopamine receptor agonist, quinpirole (0.0, 0.3, or 3.0 mg/kg), and/or the D1-type dopamine receptor antagonist, SCH 23390 (0.0 or 0.5 mg/kg) for 8-10 days. After each daily injection, the rats were tested for locomotor activity in photocell arenas for 20 min. Following this subchronic pretreatment, all rats were challenged with the mixed dopamine receptor agonist apomorphine (1.0 mg/kg, SC) and tested for locomotor activity. SKF 38393 treatments produced a dose-dependent decrease in locomotor activity which did not significantly change across days. Quinpirole also depressed locomotor activity when first injected, but this quinpirole-induced inhibition of activity progressively decreased across days. When subsequently challenged with apomorphine, rats in both the SKF 38393 and the quinpirole pretreatment groups displayed greater locomotor activity than rats pretreated with only vehicle. Although SCH 23390 pretreatments did not affect subsequent sensitivity to apomorphine, SCH 23390 completely blocked the effect of quinpirole. These results suggest that although repeated D1 receptor stimulation may be sufficient to induce behavioral sensitization to apomorphine, D2 receptor stimulation also contributes to the effect.