MESENCEPHALIC GRAFTS PARTIALLY RESTORE NORMAL NIGRAL DYNORPHIN LEVELSIN 6-HYDROXYDOPAMINE-LESIONED RATS TREATED CHRONICALLY WITH L-DIHYDROXYPHENYLALANINE

An increase of dynorphin levels is commonly observed in the substantia nigra of 6-hydroxydopamine-lesioned rats chronically treated with dai ly injections of L-DOPA. This study investigates the potential of feta l mesencephalic grafts to restore normal levels of dynorphin in such c ases. After 19 consecutive days of treatment with L-DOPA, lesioned rat s with the most severe nigral cell loss showed increased levels of dyn orphin in the substantia nigra ipsilateral to the lesion, as expected. The changes were assessed by standard immunohistochemical techniques combined with the use of an image analysis system. Such changes were n ot observed in the substantia nigra of rats that received fetal mesenc ephalic cells in the striatum six months prior to the beginning of the chronic treatment. However, only animals displaying heavy loss of dop aminergic neurons in the substantia nigra pars compacta showed signifi cant changes of dynorphin levels in the substantia nigra following dru g treatment. Our results show that fetal nigral cells transplanted int o the striatum have the potential to prevent biochemical changes obser ved in the basal ganglia induced by the lesion of the nigrostriatal pa thway and chronic treatment with L-DOPA. It is still hypothesized from studies in rodents that this peptide may play a role in the appearanc e of DOPA-induced dyskinesia, because dynorphin levels increase in the substantia nigra pars reticulata after L-DOPA treatment. If this happ ens to be the case, then the use of fetal nigral grafts could therefor e be an important step to prevent the induction of dyskinesia after ch ronic L-DOPA treatment.