Levodopa induces a cytoplasmic localization of D1 dopamine receptors in striatal neurons in Parkinson's disease

Parkinson's disease is characterized by a massive loss of nigral dopamine n eurons that results in a reduction of dopamine concentrations in the striat um. The most commonly used treatment for this disease is levodopa therapy t o restore striatal dopamine. This treatment is mediated by dopamine recepto rs, but the effect of treatment and the disease on receptor distribution is unknown. In this study, the distribution of D1 dopamine receptors was anal yzed at the cellular and subcellular level in the striatum of 5 patients wi th Parkinson's disease (all treated with levodopa) and 4 control subjects. In the control brains, D1 dopamine receptors were mostly detected on the pl asma membrane of medium-sized spiny neurons. The quantitative analysis perf ormed at the ultrastructural level in patients with Parkinson's disease rev ealed an increase in immunostaining in the cytoplasm of medium-sized neuron s. This effect was likely the result of the treatment rather than the dopam inergic denervation, as such changes were not observed in the striatum of r ats with a unilateral 6-hydroxydopamine nigrostriatal lesion, but were pres ent in normal or lesioned rats treated with a D1 dopamine agonist. Altered localization of D1 dopamine receptors may participate in the occurrence of side effects of levodopa therapy such as dyskinesia and fluctuations in mot or performances.