CHRONIC TREATMENT WITH LEVODOPA AND OR SELEGILINE DOES NOT AFFECT BEHAVIORAL RECOVERY INDUCED BY FETAL VENTRAL MESENCEPHALIC GRAFTS IN UNILATERALLY 6-HYDROXYDOPAMINE-LESIONED RATS/

It has been suggested that levodopa (L-dopa), a dopamine precursor use d to treat Parkinson's disease, may be toxic to grafted fetal neurobla sts; if so, the use of the monoamine oxidase B inhibitor selegiline mi ght prevent such toxicity. We randomly assigned 30 unilaterally 6-hydr oxydopamine-lesioned male Sprague-Dawley rats, whose lesions were veri fied with low-dose apomorphine-induced rotations, to one of five treat ment groups: (i) L-dopa methyl ester (125 mg/kg/day) with benserazide (a peripheral decarboxylase inhibitor; 25 mg/kg/day), (ii) L-dopa meth yl ester with benserazide and selegiline (L-deprenyl; 0.5 mg/kg/day), (iii) selegiline only, (iv) and (v) vehicle (ascorbate in normal salin e) only. After 2 weeks of twice-daily ip injections, the rats received fetal ventral mesencephalic grafts into the lesioned striatum; one ve hicle group received sham grafts. Drug therapy was contin ued for 21/2 months post grafting. At 1 month after grafting, and every 2 weeks th ereafter, the rats were tested using low-dose apomorphine-induced rota tion. A 70% decrease in rotations among all grafted groups, relative t o the shams, was found. No statistical differences among groups receiv ing various drug therapies were seen in behavior or in counts or dimen sions of tyrosine hydroxylase-positive cells. We therefore conclude th at, in the unilaterally lesioned rat model of Parkinson's disease, the re is no adverse effect of L-dopa nor any significant effect of selegi line, either alone or coadministered with L-dopa, on behavioral recove ry induced by fetal ventral mesencephalic grafts. (C) 1994 Academic Pr ess, Inc.