No functional effects of embryonic neuronal grafts on motor deficits in a 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy)

lntrastriatal injection of 3-nitropropionic acid results in secondary excit otoxic local damage and retrograde neuronal cell loss in substantia nigra p ars compacta, thus mimicking salient features of striatonigral degeneration , the core pathology underlying Parkinsonism associated with multiple syste m atrophy. We used 3-nitropropionic acid to create a rat model of advanced striatonigral degeneration in order to assess the effects of embryonic allo grafts upon rotational and complex-motor behavioural abnormalities. Followi ng stereotaxic intrastriatal administration of 500 nmol 3-nitropropionic ac id in male Wistar rats we observed consistent amphetamine- and apomorphine- induced ipsiversive rotation. Furthermore, there were marked deficits of co ntralateral paw reaching. Subsequently, animals received intrastriatal impl antations of either E14 mesencephalic or striatal or mixed embryonic cell s uspensions. In addition, one group received sham injections. Grafted rats w ere followed for up to 21 weeks and repeated behavioural tests were obtaine d during this period. Drug-induced rotation asymmetries and complex motor d eficits measured by paw reaching tests were not compensated by embryonic gr afts. persistence of drug-induced rotations and of paw reaching deficits fo llowing transplantation probably reflects severe atrophy of adult striatum, additional nigral degeneration as well as glial demarcation of embryonic g rafts. We suggest that dopamine rich embryonic grafts fail to induce functional re covery in a novel 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy). (C) 2001 IBRO. Published by Elsevi er Science Ltd. All rights reserved.