Neurochemical and Behavioral Studies on L-dopa Toxicity in the Model of Manganese Lesioned Nigrostriatal Pathway in the Rat: Evidence for a Protective Effect of the GM1 Lactone Siagoside

Publisher Summary This chapter discusses the neurochemical and behavioral studies on L-dopa toxicity in the model of manganese kesioned nigrostriatal pathway in the rat. Evidence was obtained with in vitro studies of a toxic action of L-dopa on neuroblastoma cells, evaluated as [ 3 H]-thymidine uptake and cell survival. It was found that the chronic administration of L-dopa to normal adult rats or mice did not lead to nigral cell disappearance and did not endanger the survival of foetal ventral mesencephalic grafts inplanted in 6-OHDA lesioned striatum. Accordingly, studies performed on humans did not give evidence of the histological signs of L-dopa toxicity in normal subjects or in Parkinsonian patients. However, some clinical trials suggest that the wearing-off phenomenon, tardive dyskinesia, and on–off phenomena are the possible side effects of long-term L-dopa treatment. Apart from human studies, experiments on the in vivo toxicity of L-dopa were performed in unlesioned mice or rats and on foetal grafts in 6-OHDA lesioned rats suggesting a lack of any effect of L-dopa chronic administration on cell survival.