DOPAMINERGIC MICROTRANSPLANTS INTO THE SUBSTANTIA-NIGRA OF NEONATAL RATS WITH BILATERAL 6-OHDA LESIONS .II. TRANSPLANT-INDUCED BEHAVIORAL RECOVERY

Transplants of fetal ventral mesencephalic (VM) dopamine neurons impla nted into the substantia nigra in 6-hydroxydopamine (6-OHDA)-lesioned neonatal pups establish axonal connections with the denervated caudate putamen (Nikkhah et al., 1995), In the present study, we have explore d the functional capabilities of these animals after they reached adul thood on a battery of spontaneous and drug-induced behavioral tasks, T he results demonstrate that unilateral intranigral VM grafts in bilate rally lesioned neonates induce a marked bias in spontaneous- and stres s-induced rotation contralateral to the implant not present in the les ion-only controls, Amphetamine and apomorphine induced vigorous contra - and ipsilateral rotation, respectively, Moreover, grafted animals ac hieved 75% of the performance level in contralateral skilled forelimb use when compared to normal controls, which was significantly above le sion-only animals (50% of normal), Spontaneous nocturnal locomotor act ivity was elevated 2.2-fold in the grafted animals, Sensorimotor orien tation and disengage behavior was spared by the neonatal dopamine lesi on and unaffected by the grafts. The level of functional restoration s een in the present study was more extensive than reported previously i n neonatally 6-OHDA-lesioned rats where the VM grafts were implanted e ctopically into the striatum, However, functional recovery remained in complete also after intranigral graft placement compared to normal int act animals, The present approach should provide a new promising avenu e for the continued exploration of the mechanisms involved in function al recovery and structural repair in the damaged nigrostriatal system.