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However, in vivo evidence of levodopa toxicity is scarce. We have evaluated the effects of a 6\u2010month oral levodoapa treatment on several dopaminergic markers, in rats with moderate or severe 6\u2010hydroxydopamine\u2010induced lesions of mesencephalic dopamine neurons and sham\u2010lesioned animals. Counts of tyrosine hydroxylase (TH)\u2010immunoreactive neurons in the substantia nigra and ventral tegmental area showed no significant difference between levodopa\u2010treated and vehicle\u2010treated rats. In addition, for rats of the sham\u2010lesioned and severely lesioned groups, immunoradiolabeling for TH, the dopamine transporter (DAT), and the vesicular monoamine transporter (VMAT2) at the striatal level was not significantly defferent between rats treated with levodopa or vehicle. It was unexpected that quantification of immunoautoradiograms showed a partial recovery of all three dopaminergic markers (TH, DAT, and VMAT2) in the denervated territories of the striatum of moderately lesioned rats receiving levodopa. Furthermore, the density of TH\u2010positive fibers observed in moderately lesioned rats was higher in those treated chronically with levodopa than in those receiving vehicle. Last, that chronic levodopa administration reversed the up\u2010regulation of D2 dopamine receptors seen in severely lesioned rats provided evidence that levodopa reached a biologically active concentration at the basal ganglia. Our results demonstrate that a pharmacologically effective 6\u2010month oral levodopa treatment is not toxic for remaining dopamine neurons in a rat model of PD but instead promotes the recovery of striatal innervation in rats with partial lesions.<\/jats:p>","DOI":"10.1002\/ana.410430504","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:15:36Z","timestamp":1104592536000},"page":"561-575","source":"Crossref","is-referenced-by-count":182,"title":["Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions"],"prefix":"10.1002","volume":"43","author":[{"given":"M. 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