L-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of parkinson's disease: relation to motor and cellular parameters of nigrostriatal function.

摘要: In order to assess the role of striatal dopamine (DA) afferents in L-DOPA-induced dyskinesia, we have studied a large series rats sustaining 2, 3, or 4 unilateral injections 6-hydroxydopamine (6-OHDA) lateral striatum. This type lesion produced dose-dependent depletion DA fibers caudate-putamen, which was most pronounced aspects this structure. An additional group injected with 6-OHDA medial forebrain bundle obtain complete denervation on one side brain. During course chronic L-DOPA treatment, intrastriatal lesions developed abnormal involuntary movements (AIMs), mapped onto domains exhibiting at least approximately 90% denervation, as judged by transporter autoradiography. The denervated areas showed local upregulation preproenkephalin and prodynorphin mRNA, FosB-like immunoreactivity, were highly correlated rats' AIM scores. When compared completely DA-denervated animals, an overall lower incidence, severity different topographic distribution AIMs. involvement proximal limb axial muscles proportional spreading from towards caudate-putamen. Locomotive AIMs only seen lesions, but not any animals (which > 5% fiber sparing striatum). Intrastriatally 6-OHDA-lesioned had larger therapeutic window for than did since they exhibited predisposition dyskinesia similar degree drug-induced motor improvement test forelimb stepping. Our results are first demonstrate that selective partial sensorimotor part striatum can confer cellular behavioral supersensitivity L-DOPA, phenomenology rat be accounted topography within