Dopamine-rich grafts alleviate deficits in contralateral response space induced by extensive dopamine depletion in rats
Author
Heuer, Andreas
Lelos, Mariah
Kelly, Claire
Torres, Eduardo
Dunnett, Stephen
Date
2013Type
Article
Publisher
Elsevier
ISSN
0014-4886
Metadata
Show full item recordAbstract
Unilateral infusion of 6-hydroxydopamine into the nigro-striatal pathway in the rat is the most common dopamine
lesion model of Parkinson's disease. In the present study, we explore the impact of near complete
unilateral loss of dopamine along the nigro-striatal pathway and subsequent cell replacement therapy in a
choice reaction time task in rats, with assessment of spatial responding towards either side of the body
(ipsilateral or contralateral to the lesion) on alternate days. Results indicated a stable contralateral deficit
in response accuracy, reaction times and motor function for 50 consecutive days of testing, with no signs
of recovery or compensation. All lesioned rats developed a near-hole bias and displayed prolonged movement
and reaction times when responses had to be directed towards a distal response location on the side
of the body contralateral to the lesion, as well as a smaller ipsilateral impairment in response accuracy and
movement times. Grafts of dopamine-rich tissue into the denervated striatum improved some, but not all,
of the deficits induced by the lesion. Specifically, grafted rats performed at a similar level to control animals
when assessed on the ipsilateral side, they demonstrated a partial restitution of their ability to respond to far
contralateral stimuli, and they exhibited a marked reduction in the time to complete all lateralised responses
on both sides. The present characterisation of the task and the effects of cell replacement via primary fetal
mesencephalic tissue demonstrate restorative properties in alleviating the marked spatial response bias
induced by unilateral loss of dopamine.
© 2013 Elsevier Inc. All rights reserved.
Journal/conference proceeding
Experimental Neurology;
Citation
Experimental Neurology 247 (2013) 485–495
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