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Journal of Neuroscience, Vol 15, 3863-3875, Copyright © 1995 by Society for Neuroscience
Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test
M Olsson, G Nikkhah, C Bentlage and A Bjorklund
Department of Medical Cell Research, University of Lund, Sweden.
Methods for the assessment of akinesia in the unilateral rat Parkinson
model have so far been lacking. The experiments reported here evaluate the
usefulness of a new "stepping test" to monitor forelimb akinesia in rats
with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic
dopamine (DA) system, and to assess the ability of DA- receptor agonists
and fetal DA neuron transplants to reverse these deficits. The 6-OHDA
lesion induced marked and long-lasting impairments in the initiation of
stepping movements with the contralateral paw. Systemic injections of low
doses (chosen to be subthreshold for induction of rotation) of the mixed D1
and D2 receptor agonist apomorphine, the D1-selective agonist SKF 38393,
and to a lesser extent also the D2-selective agonist quinpirole were
effective in reversing these deficits. Similar effects was seen after a
subrotational dose of L-dopa, whereas amphetamine had no effect. Fetal
nigral transplants, implanted as multiple deposits in the ipsilateral
caudate-putamen and substantia nigra, restored initiation of stepping to a
similar degree as the DA agonists. Nigral grafts placed in substantia nigra
alone were also effective, although the improvement was less pronounced.
Apomorphine, at a dose effective in the lesion-only animals, had no
additive effect in the grafted rats, whereas amphetamine appeared to
further improve stepping in the rats with intranigral transplants.
Identical experiments were performed on skilled forelimb use in the so-
called staircase test. Interestingly, neither the DA agonist drugs nor the
nigral transplants had any effects on the lesion induced deficits in this
more complex task. The results show that forelimb stepping is a highly
useful test to monitor lesion-/and transplant-induced changes in forelimb
akinesia, a behavioral parameter that may be analogous to limb akinesia and
gait problems seen in patients with Parkinson's disease.
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