Differential effect of repeated treatment with l-DOPA on dopamine-D1 or -D2 receptors

Unilateral degeneration of the nigro-striatal dopaminergic pathway with 6-hydroxydopamine induced controlateral rotations to apomorphine injection, increased [³H]spiroperidol binding and enhanced sensitivity of adenylate cyclase to dopamine stimulation in lesioned striata. Prolonged L-DOPA administration counteracted the increased density of [3H]-spiroperidol binding sites but further enhanced the hypersensitivity of adenylate cyclase to dopamine. Also apomorphine-induced controlateral rotations were potentiated. This effect was antagonized by SCH-23390. These results suggest that dopaminergic D1 and D2 receptors are differently affected by prolonged L-DOPA treatment. This study was supported by grants from Italian CNR and MPI.