EFFECT OF L-DOPA ALONE AND WITH BENSERAZIDE ON THE SPONTANEOUS ACTIVITY OF STRIATAL NEURONS IN NORMAL AND 6-HYDROXYDOPAMINE-LESIONED RATS

1 The effects of L-dopa methylester (LDME), an analogue of levodopa, o n the spontaneous activity of dopamine sensitive neurones in the rat s triatum, after B-hydroxydopamine induced degeneration of the nigrostri atal tract were compared with those in unlesioned animals both in the absence and presence of benserazide, a peripheral DOPA decarboxylase i nhibitor (PDI). 2 Studies were performed at 5-7 days post lesion (grou p 1 animals), at 21 days (group 2) when denervation supersensitivity w as evident ty contralateral turning to apomorphine and at the same tim e but following 7 days dosing with LDME plus benserazide (group 3). 3 In unlesioned animals, LDME alone inhibited spontaneous firing by some 45% over 60 min including a marked but transient early phase which wa s still present in all lesioned animals even though the later inhibiti on was significantly reduced in group 1 and 3 animals. 4 When given af ter benserazide in unlesioned animals LDME still produced a similar le vel of overall inhibition but without the early phase. The lesion redu ced the overall inhibition, except in group 2 animals, and after chron ic dosing (group 3) it was almost absent. 5 It is proposed that since the early inhibition with LDME alone is still seen after lesion of the nigrostriatal tract but not after the PDI benserazide, it is caused. by peripherally formed dopamine and that as the delayed inhibition wit h LDME alone and after benserazide are all reduced by nigrostriatal le sions, as is its amphetamine like ipsilateral turning, that this depen ds on locally (striatal) synthesized dopamine. 6 This study also shows that chronic levodopa/PDI treatment reduces the compensating increase d activity of surviving dopaminergic neurones and the functional super sensitivity to dopamine suggests that the long term administration of levodopa may reduce its own utilization and activity in the striatum a nd in the treatment of Parkinson's Disease.