Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/63450
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Genetic Inactivation of Dopamine D1 but Not D2 Receptors Inhibits L-DOPA-Induced Dyskinesia and Histone Activation |
Autor: | Darmopil, Sanja CSIC; Martín- Hernández, A. B.; Diego, I. R.; Ares-Santos, Sara CSIC ORCID; Moratalla, Rosario CSIC ORCID | Fecha de publicación: | 2009 | Editor: | Elsevier | Citación: | Biological Psychiatry 66: 603- 613 (2009) | Resumen: | Background: Pharmacologic studies have implicated dopamine D1-like receptors in the development of dopamine precursor molecule 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesias and associated molecular changes in hemiparkinsonian mice. However, pharmacologic agents for D1 or D2 receptors also recognize other receptor family members. Genetic inactivation of the dopamine D1 or D2 receptor was used to define the involvement of these receptor subtypes. Methods: During a 3-week period of daily L-DOPA treatment (25 mg/kg), mice were examined for development of contralateral turning behavior and dyskinesias. L-DOPA-induced changes in expression of signaling molecules and other proteins in the lesioned striatum were examined immunohistochemically. Results: Chronic L-DOPA treatment gradually induced rotational behavior and dyskinesia in wildtype hemiparkinsonian mice. Dyskinetic symptoms were associated with increased FosB and dynorphin expression, phosphorylation of extracellular signal-regulated kinase, and phosphoacetylation of histone 3 (H3) in the lesioned striatum. These molecular changes were restricted to striatal areas with complete dopaminergic denervation and occurred only in dynorphin-containing neurons of the direct pathway. D1 receptor inactivation abolished L-DOPA-induced dyskinesias and associated molecular changes. Inactivation of the D2 receptor had no significant effect on the behavioral or molecular response to chronic L-DOPA. Conclusions: Our results demonstrate that the dopamine D1 receptor is critical for the development of L-DOPA-induced dyskinesias in mice and in the underlying molecular changes in the denervated striatum and that the D2 receptor has little or no involvement. In addition, we demonstrate that H3 phosphoacetylation is blocked by D1 receptor inactivation, suggesting that inhibitors of H3 acetylation and/or phosphorylation may be useful in preventing or reversing dyskinesia. © 2009 Society of Biological Psychiatry. | URI: | http://hdl.handle.net/10261/63450 | DOI: | 10.1016/j.biopsych.2009.04.025 | Identificadores: | doi: 10.1016/j.biopsych.2009.04.025 issn: 0006-3223 |
Aparece en las colecciones: | (IC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
221
checked on 20-abr-2024
WEB OF SCIENCETM
Citations
207
checked on 23-feb-2024
Page view(s)
330
checked on 22-abr-2024
Download(s)
125
checked on 22-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.