LEVODOPA BIOTRANSFORMATION IN HEMI-PARKINSON RATS - EFFECT OF DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS

We investigated the effects of continuous perfusion of dopamine D-1 an d D-2 receptor agonists and antagonists on the biotransformation of lo cally applied levodopa (L-DOPA) to dopamine in the striatum of freely moving hemi-Parkinson rats by means of in vivo microdialysis. The exte nt of the lesion was shown to influence dopamine formation after L-DOP A administration. In partially denervated striatum there was a more 'p hysiological' conversion, whereas in extensively denervated striatum e xtracellular dopamine increased to excessively high levels after L-DOP A. The dopamine D-2 receptor agonist quinpirole (10 mu M) attenuated t he L-DOPA-induced (2 mu M) dopamine release in intact, partially dener vated and extensively denervated striatum. The dopamine D-1 receptor a ntagonist SCH 23390 hyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine hydrochloride) (10 mu M) caused effects similar to those of quinpirol e. However, in intact striatum it acted as the dopamine D-2 receptor a ntagonist (-)-sulpiride and the dopamine D-1 receptor agonist CY 20824 3 exahydro-7-methyl-indolo-(4,3-ab)phenanthoridine), showing no effect on L-DOPA biotransformation. The data suggest that dopamine D-2 recep tor agonists and possibly dopamine D-1 receptor antagonists will be be neficial in the treatment of Parkinson's disease, probably by keeping extracellular levels of dopamine at more 'physiological' levels. This may enable a reduction of L-DOPA doses and therefore may prevent dyski nesias at a later stage of the disease.