EARLY GESTATIONAL MESENCEPHALON GRAFTS, BUT NOT LATER GESTATIONAL MESENCEPHALON, CEREBELLUM OR SHAM GRAFTS, INCREASE DOPAMINE IN CAUDATE-NUCLEUS OF MPTP-TREATED MONKEYS

The mechanism of the behavioral improvement observed in parkinsonian p rimates that receive intrastriatal transplants of fetal dopamine neuro ns has not been firmly established. Dopamine production by grafted neu rons may be the basis of the behavioral recovery. Alternatively, stimu lation of the host dopamine system by the transplant procedure itself may be central to the outcome. The present study examined whether dopa mine concentration was raised in the caudate nucleus of the 1-methyl-4 -phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primate following gr afting, and if so, whether the elevation was dependent on either (i) t he introduction of the implantation cannula (sham), (ii) the brain reg ion that was grafted, or (iii) the gestational age of fetal tissue tha t was grafted. Transplantation of early gestational age fetal ventral mesencephalon (embryonic days 40-50) was associated with significant e levation of caudate nucleus dopamine concentration to a mean of approx imately 20% of control values in the vicinity (within 2 mm) of the gra ft, compared with more distant sites in the caudate nucleus. With earl y gestational age fetal ventral mesencephalon, the ratio of homovanill ic acid/dopamine concentration near the graft site was normalized comp ared to the elevated value found in the caudate nucleus distant from t he graft site. Grafts of later stage fetal ventral mesencephalon, or f etal cerebellum or sham implantation did not increase dopamine concent ration or lower homovanillic acid/dopamine ratio near the graft site. Biochemical and histochemical evidence suggests that host dopamine neu rons terminating in the nucleus accumbens are not the source of the ch anges. Numerous tyrosine hydroxylase-positive neurons at the graft sit e were only observed in the MPTP-treated monkeys that received grafts of early gestational age fetal ventral mesencephalon. These data lend strong support to the hypothesis that dopamine derived from grafted do pamine neurons is the major basis for behavioral recovery observed fol lowing intrastriatal transplantation in our MPTP-treated monkeys.