Effects of chronic SCH 23390 treatment on dopamine autoreceptor function in rat brain

The effects of chronic treatment with SCH 23390 (0.5 mg/kg per day, 18 days), a selective (DA) D-1 receptor antagonist, on dopamine autoreceptor function in rats were investigated. The decrease of DA metabolism in mesolimbic and nigrostriatal systems and inhibition of spontaneous explorative locomotor activity by low doses of the selective D-2 receptor agonist, quinpirole, were used as behavioral and biochemical indices of DA autoreceptor function. The DA metabolism decreasing effect of quinpirole (20 and 50 micrograms/kg) in mesolimbic or nigrostriatal DA systems was similar in SCH 23390- and vehicle-treated rats. Two-way analysis of variance showed that rats treated chronically with SCH 23390 were significantly more active than vehicle-treated rats. However, there were no statistically significant differences in the quinpirole-induced hypomotility response between these groups. These results indicate that chronic D-1 blockade, unlike classical antipsychotic drugs, does not modulate the biochemical and behavioral indices of DA autoreceptor activation, suggesting a lack of interaction between DA autoreceptors and D-1 receptors in the central nervous system.