Journal of Neuroscience, Vol 15, 3562-3570, Copyright © 1995 by Society for Neuroscience
Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. II. Transplant-induced behavioral recovery
G Nikkhah, MG Cunningham, R McKay and A Bjorklund
Department of Medical Cell Research, University of Lund, Sweden.
Transplants of fetal ventral mesencephalic (VM) dopamine neurons implanted
into the substantia nigra in 6-hydroxy-dopamine (6-OHDA)- lesioned neonatal
pups establish axonal connections with the denervated caudate putamen
(Nikkhah et al., 1995). In the present study, we have explored the
functional capabilities of these animals after they reached adulthood on a
battery of spontaneous and drug-induced behavioral tasks. The results
demonstrate that unilateral intranigral VM grafts in bilaterally lesioned
neonates induce a marked bias in spontaneous- and stress-induced rotation
contralateral to the implant not present in the lesion-only controls.
Amphetamine and apomorphine induced vigorous contra- and ipsilateral
rotation, respectively. Moreover, grafted animals achieved 75% of the
performance level in contralateral skilled forelimb use when compared to
normal controls, which was significantly above lesion-only animals (50% of
normal). Spontaneous nocturnal locomotor activity was elevated 2.2-fold in
the grafted animals. Sensorimotor orientation and disengage behavior was
spared by the neonatal dopamine lesion and unaffected by the grafts. The
level of functional restoration seen in the present study was more
extensive than reported previously in neonatally 6-OHDA-lesioned rats where
the VM grafts were implanted ectopically into the striatum. However,
functional recovery remained incomplete also after intranigral graft
placement compared to normal intact animals. The present approach should
provide a new promising avenue for the continued exploration of the
mechanisms involved in functional recovery and structural repair in the
damaged nigrostriatal system.
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