Intrastriatal Dopamine Infusion Reverses Compensatory Increases in D2-Dopamine Receptors in the 6-OHDA Lesioned Rat

Abstract

Direct infusion of dopamine into the corpus striatum has been proposed as a potential approach for the treatment of Parkinson's disease. The present study examined the effect of intrastriatal dopamine infusion on D₂-dopamine receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat brain. The completeness of the 6-OHDA-induced nigrostriatal injury was confirmed using [³H]-mazindol autoradiography and apomorphine-induced behaviour. Intrastriatal infusion of three different dopamine doses significantly reduced the apomorphine-induced behaviour. [³H]-spiperone autoradiography performed one day after the termination of dopamine infusion into the striatum revealed a dramatic reduction of D₂-dopamine receptor binding. The mean ± SEM percent reduction of D₂receptor binding in the affected areas of the striatum was 28.8±1.0% for 4.74 μg dopamine/h infusion rate, 35.0 ± 1.6% for 9.48 μg dopamine/h infusion rate and 33.3 ± 5.0% for 14.22 μg dopamine/h infusion rate when compared to the unlesioned side. Infusion of vehicle alone did not have any effect. The present results support the concept that intrastriatal dopamine infusion may be a useful therapeutic approach for the treatment of Parkinson's disease.