| First Author | Solís O | Year | 2017 |
| Journal | Cereb Cortex | Volume | 27 |
| Issue | 1 | Pages | 435-446 |
| PubMed ID | 26483399 | Mgi Jnum | J:255456 |
| Mgi Id | MGI:6107658 | Doi | 10.1093/cercor/bhv231 |
| Citation | Solis O, et al. (2017) Dopamine D3 Receptor Modulates l-DOPA-Induced Dyskinesia by Targeting D1 Receptor-Mediated Striatal Signaling. Cereb Cortex 27(1):435-446 |
| abstractText | The dopamine D3 receptor (D3R) belongs to the dopamine D2-like receptor family and is principally located in the ventral striatum. However, previous studies reported D3R overexpression in the dorsal striatum following l-DOPA treatment in parkinsonian animals. This fact has drawn attention in the importance of D3R in l-DOPA-induced dyskinesia (LID). Here, we used D3R knockout mice to assess the role of D3R in LID and rotational sensitization in the hemiparkinsonian model. Mice lacking D3R presented a reduction in dyskinesia without interfering with the antiparkinsonian l-DOPA effect and were accompanied by a reduction in the l-DOPA-induced rotations. Interestingly, deleting D3R attenuated important molecular markers in the D1R-neurons such as FosB, extracellular signal-regulated kinase, and histone-3 (H3)-activation. Colocalization studies in D1R-tomato and D2R-green fluorescent protein BAC-transgenic mice indicated that l-DOPA-induced D3R overexpression principally occurs in D1R-containing neurons although it is also present in the D2R-neurons. Moreover, D3R pharmacological blockade with PG01037 reduced dyskinesia and the molecular markers expressed in D1R-neurons. In addition, this antagonist further reduced dyskinetic symptoms in D1R heterozygous mice, indicating a direct interaction between D1R and D3R. Together, our results demonstrate that D3R modulates the development of dyskinesia by targeting D1R-mediated intracellular signaling and suggest that decreasing D3R activity may help to ameliorate LID. |
