MODULATION OF LEVODOPA-INDUCED MOTOR RESPONSE COMPLICATIONS BY NMDA ANTAGONISTS IN PARKINSONS-DISEASE

Citation
Pj. Blanchet et al., MODULATION OF LEVODOPA-INDUCED MOTOR RESPONSE COMPLICATIONS BY NMDA ANTAGONISTS IN PARKINSONS-DISEASE, Neuroscience and biobehavioral reviews, 21(4), 1997, pp. 447-453
Citations number
80
Categorie Soggetti
Neurosciences,"Clinical Neurology","Behavioral Sciences
ISSN journal
01497634
Volume
21
Issue
4
Year of publication
1997
Pages
447 - 453
Database
ISI
SICI code
0149-7634(1997)21:4<447:MOLMRC>2.0.ZU;2-P
Abstract
The complex dopamine-glutamate interactions within the basal ganglia a re disrupted by chronic nigrostriatal denervation and standard replace ment therapy with levodopa. Acute N-methyl-D-aspartate (NMDA) receptor blockade is able to overcome the changes in dopamine D-1- and D-2-dep endent responses and the progressive shortening in the duration of res ponse induced by long-term exposure to levodopa in 6-hydroxydopamine-l esioned rats. Preliminary results further suggest that NMDA receptor b lockade can counteract levodopa-induced dyskinesias in ethyl-4-phenyl- 1,2,3,6-tetrahydropyridine-lesioned non-human primates and parkinsonia n patients without substantially altering the motor benefit derived fr om levodopa. These results appear to be in accordance with our 2-deoxy glucose studies in 6-hydroxydopamine-lesioned rats showing that NMDA r eceptor blockade can attenuate many of the changes in synaptic activit y induced by levodopa, particularly in the striatopallidal complex. Ta ken together, our observations suggest that abnormal glutamate transmi ssion or dysregulation of NMDA receptor-mediated mechanisms contribute to levodopa-induced motor response complications. Additional preclini cal and clinical experiments need to be completed with well tolerated glutamate antagonists to determine the full potential of glutamate rec eptor blockade as a long-term strategy against levodopa-related motor response complications in Parkinson's disease. (C) 1997 Elsevier Scien ce Ltd.