A FETAL NIGRAL GRAFT PREVENTS BEHAVIORAL SUPERSENSITIVITY ASSOCIATED WITH REPEATED INJECTIONS OF L-DOPA IN 6-OHDA RATS - CORRELATION WITH D1 AND D2 RECEPTORS

The effect of repeated administration of L-3,4-dihydroxyphenylalanine was studied behaviorally and biochemically in grafted versus non-graft ed rats with a 6-hydroxydopamine unilateral lesion of the dopaminergic nigro-striatal pathway. Non-grafted rats receiving 14 injections of L -3,4-dihydroxyphenylalanine increased their contraversive circling whi le grafted rats did not, even after fourteen injections. The density o f striatal dopamine receptors was examined by autoradiography using th e ligands [H-3]-SCH 23390 for dopamine D1 receptors and [H-3]-spiperon e for D2 receptors. In rats with a lesion of the nigro-striatal dopami nergic pathway, an increase of [H-3]-SCH 23390 and [H-3]-spiperone bin ding in the lesioned striatum was observed when compared with the stri atum on the intact side. Chronic treatment with L-3,4-dihydroxyphenyla lanine led to a further increase in D1 receptor density in the lesione d as well as the intact side. A similar pattern was observed for D2 re ceptors although the change did not reach significance. A graft of fet al nigral neurons brought the density of both D1 and D2 receptors on t he lesioned side back to the level of the intact side. This is observe d both in acutely or chronically L-3,4-dihydroxyphenylalanine treated rats. This study suggests that nigral grafts protect the striatum agai nst L-3,4-dihydroxyphenylalanine-induced supersensitivity. It appears that the graft preserves the symmetry of the striatum even though ther e is an increase of D1 dopamine receptors. These results suggest that a fetal nigral graft could prevent the induction of 3-4-dihydroxypheny lalanine- induced dyskinesia in parkinsonian patients.