Role of nigral lesion in the genesis of dyskinesias in a rat model of Parkinson's disease.
The pathogenesis of the motor fluctuations and dyskinesias that complicate levodopa treatment for Parkinson's disease (PD) remains uncertain. To evaluate the relationship between the degree of dopamine neuron loss and the severity of dyskinesias in a rodent model of PD, Sprague-Dawley rats were lesioned unilaterally using different doses of 6-hydroxydopamine injected into the substantia nigra pars compacta (SNc). All rats received two daily oral doses of levodopa for one month. In most of the animals chronic levodopa administration induced abnormal involuntary movements (AIMs), which were in some respects similar to human dyskinesias. We found that a minimum dopamine cell loss of around 95% was required for the development of dyskinesias after one-month of levodopa treatment. Moreover, we observed a positive relationship between the percentage dopaminergic cell loss in the SNc and the severity of levodopa-induced AIMs.
Paillé
Vincent
V
INSERM, Unité 437, CHU de Nantes, 30 bd Jean Monnet, 44093 Nantes, France. vpaille@nantes.inserm.fr
Brachet
Philippe
P
Damier
Philippe
P
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D020820:Dyskinesias / Q000503:physiopathology*; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000473:pathology / Q000503:physiopathology*; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000978:Antiparkinson Agents; D013565:Sympatholytics; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase