DOPAMINERGIC TRANSPLANTS SUPPRESS L-DOPA-INDUCED FOS EXPRESSION IN THE DOPAMINE-DEPLETED STRIATUM IN A RAT MODEL OF PARKINSONS-DISEASE

We examined the effects of MK-801, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and fetal ventral mesencephalic (VM) transplants on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced Fos protein expression in the dopamine (DA)-depleted striatum. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were produced in young adult female rats and grafting was performed 3 weeks later. Methamphetamine-induced rotational behavior recovered signific antly on the 4th week after grafting. Immunohistochemical examinations of c-Fos and tyrosine hydroxylase (TH) were performed 3-4 months afte r grafting. L-DOPA (100 mg/kg, i.p.) markedly induced Fos-like immunor eactivity (FLI) in the DA-depleted striatum. Pretreatment with a large dose of MK-801 (3-4.5 mg/kg, i.p.) dose-dependently suppressed L-DOPA -induced FLI in the striatum. The stimulatory effect of L-DOPA on c-Fo s expression observed within the lesioned striatum was suppressed by f etal VM transplants. It seemed that the graft-induced effect on FLI ex tended over a considerably larger area than that covered by the graft- derived TH-immunoreactive innervation. Taken together, these findings suggest that glutamatergic modulation is involved in the L-DOPA-induce d c-Fos expression in the denervated striatum which is normalized by f etal VM transplants. It also seems likely that VM grafts suppress the L-DOPA-induced expression of transcriptional factors which might be in volved in the mechanisms underlying various side effects of chronic L- DOPA therapy.