Drebrin immunoreactivity in the striatum of a rat model of levodopa-induced dyskinesia.

Levodopa-induced dyskinesia has been suggested to result from maladaptive plasticity at corticostriatal synapses. Synaptic plasticity is based upon morphologic changes of dendritic spines. To elucidate whether the morphologic changes of spines occur in the striatum of rat models of levodopa-induced dyskinesia, we examined immunoreactivity of drebrin, an actin-binding protein localized in dendritic spines of excitatory synapses, using 6-hydroxydopamine-lesioned rats repeatedly treated with levodopa. The cross-sectional area of drebrin-immunoreactive organelles, putative spines, in the dopamine-denervated striatum of the levodopa-induced dyskinesia model was greater than that of the Parkinson's disease model. Immunoelectron microscopic examinations confirmed that drebrin-immunoreactive spines became enlarged in the dopamine-denervated striatum of the levodopa-induced dyskinesia model, but not in the Parkinson's disease model. These results suggest that the development of levodopa-induced dyskinesia is associated with enlargement of dendritic spines at corticostriatal excitatory synapses.