INTRASTRIATAL DOPAMINE INFUSION REVERSES COMPENSATORY INCREASES IN D-2-DOPAMINE RECEPTORS IN THE 6-OHDA LESIONED RAT

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 D-2-dopamine receptors in the 6-hydroxydopamine (6-OHDA) lesioned r at brain. The completeness of the 6-OHDA-induced nigrostriatal injury was confirmed using PH]mazindol autoradiography and apomorphine-induce d behaviour. Intrastriatal infusion of three different dopamine doses significantly reduced the apomorphine-induced behaviour. [H-3]-spipero ne autoradiography performed one day after the termination of dopamine infusion into the striatum revealed a dramatic reduction of D-2-dopam ine receptor binding. The mean +/- SEM percent reduction of D-2 recept or binding in the affected areas of the striatum was 28.8 +/- 1.0% for 4.74 mu g dopamine/h infusion rate, 35.0 +/- 1.6% for 9.48 mu g dopam ine/h infusion rate and 33.3 +/- 5.0% for 14.22 mu g dopamine/h infusi on rate when compared to the unlesioned side. infusion of vehicle alon e did not have any effect. The present results support the concept tha t intrastriatal dopamine infusion may be a useful therapeutic approach for the treatment of Parkinson's disease.