Reversal of parkinsonian symptoms by intrastriatal and systemic manipulations of excitatory amino acid and dopamine transmission in the bilateral 6-OHDA lesioned marmoset.
We have investigated the potential of alleviating parkinsonian symptoms by manipulating excitatory amino acid (EAA) transmission, by several different pharmacological means, in a novel primate model of parkinsonism. The model is based on a two-stage bilateral 6-hydroxydopamine lesion procedure in marmosets, which produces a stable but marked parkinsonian condition. Parkinsonian symptoms were reversed in a dose-dependent manner by systemic administration of levodopa and intrastriatal injections of apomorphine administered into either the caudate nucleus or the putamen. (R)-HA-966, a partial agonist for the NMDA receptor associated glycine site, also alleviated parkinsonian symptoms when injected intrastriatally but not when injected systemically. Systemic injection of enadoline, a kappa opiate which blocks release of EAAs, reduced parkinsonian symptoms when injected systemically, though it did not restore completely normal motor behaviour. In contrast, ifenprodil, an antagonist for the NMDA receptor-associated polyamine modulatory site, when injected systemically at an optimal dose, resulted in apparently normal motor behaviour. These data suggest that attenuation of EAA transmission could be used to treat parkinsonism.
Mitchell
I J
IJ
Biological Sciences, 1, 127 Stopford Building, Oxford Road, University of Manchester, Manchester M13 9PT, UK.
Hughes
N
N
Carroll
C B
CB
Brotchie
J M
JM