Archival ReportGenetic Inactivation of Dopamine D1 but Not D2 Receptors Inhibits L-DOPA–Induced Dyskinesia and Histone Activation
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Animals
This study was carried out in mice lacking D1R (15, 16, 19, 20) or D2R (21, 22, 23) generated by homologous recombination as described previously. Wildtype (WT) and homozygote D1−/− and D2−/− (knockout [KO]) mice used in this study were derived from mating heterozygous mice. Genotype was determined by polymerase chain reaction analysis. The maintenance of animals followed guidelines from European Union Council Directive (86/609/European Economic Community) and experimental protocols were
Dopamine D1, but Not D2, Receptors Are Required for Rotational Sensitization Induced by L-DOPA in Hemiparkinsonian Mice
To establish the role of the D1 and D2 dopamine receptor subtypes in the development of behavioral sensitization and dyskinesias, we used genetically engineered mice lacking either the dopamine D1 or D2 receptor. Contralateral rotations were evaluated as a measure of behavioral sensitization to L-DOPA (25 mg/kg/day) for 3 weeks (3). Twice a week, we measured the total number of contralateral turns for 120 min. We also counted the contralateral turns during the first 20 min after L-DOPA
Discussion
The findings we describe here strongly support a compulsory role for the D1R subtype in the development of dyskinesia and rotational response following L-DOPA administration as well as in the molecular changes associated with these behaviors. In contrast, the D2R appears to have little effect on any of these. We demonstrate that these L-DOPA-induced molecular changes, including the phosphoacetylation of H3, occur in the direct pathway neurons within the fully denervated region of the striatum.
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D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
2023, Neurobiology of DiseaseSelective activation of striatal indirect pathway suppresses levodopa induced-dyskinesias
2023, Neurobiology of DiseaseCitation Excerpt :Unbalanced activity between striatal pathways during dyskinesia has been described, with hyperactivity of D1-MSNs and hypoactivity of D2-MSNs (Parker et al., 2018; Ryan et al., 2018; Suárez et al., 2018). Additionally, photo- and chemostimulation of D1-MSNs elicits abnormal movements that resemble LIDs (Alcacer et al., 2017; Ryan et al., 2018; Keifman et al., 2019) while deletion of D1R abolishes them (Darmopil et al., 2009). These findings support a causal role for D1-MSNs in the expression of LIDs and suggest an imbalance between the pathways could be the crucial element.