Absence of neurotoxicity of chronic L-DOPA in 6-hydroxydopamine-lesioned rats

WE investigated the effects of 6 months' oral treatment with L-dihydroxy-phenylalanine (L-DOPA)/carbidopa on the remaining dopaminergic neurones of the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) of rats with moderate or severe 6-hydroxydopamine (6-OHDA)-induced lesions and sham-operated animals. Using a radioimmunohistochemical method we counted tyrosine hydroxylase (TH)-radioimmunoreactive cells in the SNC and the VTA in emulsion-coated sections and measured the remaining surface area of both structures on autoradiograms. The sole difference observed was a significant increase of the remaining surface area of TH radioimmunolabelling in the SNC of moderately lesioned rats treated with L-DOPA/carbidopa compared with the untreated animals, while the rest of the parameters recorded, in both structures and groups of animals, were unchanged. This suggest that in vivo, this treatment is not toxic either to healthy dopaminergic neurones of the ventral mesencephalon or to those surviving after a 6-OHDA lesion.