Site-specific action of l-3,4-dihydroxyphenylalanine in the striatum but not globus pallidus and substantia nigra pars reticulata evokes dyskinetic movements in chronic l-3,4-dihydroxyphenylalanine-treated 6-hydroxydopamine-lesioned rats

Abstract

Dyskinesia eventually develops in the majority of Parkinson's disease patients treated with l-3,4-dihydroxyphenylalanine ( l-DOPA). We have investigated the effect of an acute and local administration of l-DOPA, GABA and glutamate to provoke dyskinetic movements in three basal ganglia structures (striatum, globus pallidus (GP) and substantia nigra pars reticulata (SNr)) of chronically l-DOPA-treated, unilaterally 6-hydroxydopamine-lesioned rats. We demonstrated that l-DOPA administration into the lesioned striatum using the technique of reverse in vivo microdialysis was an effective trigger to switch on dyskinesia. Notably, local l-DOPA perfusion at the same concentration in the ipsilateral GP and SNr did not provoke significant dyskinetic behaviour. Neither GABA nor glutamate triggered dyskinetic movements in the striatum, GP or SNr. We postulate a site-specific action of l-DOPA for the evocation of already established dyskinesia since l-DOPA in the striatum but not in the GP or SNr switched on dyskinetic behaviour.