6-Hydroxydopamine lesion and levodopa treatment modif y the effect of buspirone in the substantia nigra pars reticulata
dc.contributor.author | Vegas Suárez, Sergio | |
dc.contributor.author | Pisanò, Clarissa Anna | |
dc.contributor.author | Requejo Rodríguez, Catalina | |
dc.contributor.author | Bengoetxea Odriozola, Harkaitz | |
dc.contributor.author | Lafuente Sánchez, José Vicente | |
dc.contributor.author | Morari, Michele | |
dc.contributor.author | Miguelez Palomo, Cristina | |
dc.contributor.author | Ugedo Urruela, Luisa | |
dc.date.accessioned | 2020-10-16T12:39:00Z | |
dc.date.available | 2020-10-16T12:39:00Z | |
dc.date.issued | 2020-09 | |
dc.identifier.citation | British Journal of Pharmacology 177(17) : 3957-3974 (2020) | es_ES |
dc.identifier.issn | 0007-1188 | |
dc.identifier.issn | 1476-5381 | |
dc.identifier.uri | http://hdl.handle.net/10810/46952 | |
dc.description.abstract | Background and Purpose l-DOPA-induced dyskinesia (LID) is considered a major complication in the treatment of Parkinson's disease (PD). Buspirone (5-HT(1A)partial agonist) have shown promising results in the treatment of PD and LID, however no 5-HT-based treatment has been approved in PD. The present study was aimed to investigate how thesubstantia nigra pars reticulata(SNr) is affected by buspirone and whether it is a good target to study 5-HT antidyskinetic treatments. Experimental Approach Buspirone was studied usingin vivosingle-unit, electrocorticogram, local field potential recordings along with microdialysis and immunohistochemistry in naive/sham, 6-hydroxydopamine (6-OHDA)-lesioned or 6-OHDA-lesioned andl-DOPA-treated (6-OHDA/l-DOPA) rats. Key Results Local buspirone inhibited SNr neuron activity in all groups. However, systemic buspirone reduced burst activity in 6-OHDA-lesioned rats (with or withoutl-DOPA treatment), whereas 8-OH-DPAT, a full 5-HT(1A)agonist induced larger inhibitory effects in sham animals. Neither buspirone nor 8-OH-DPAT markedly modified the low-frequency oscillatory activity in the SNr or synchronization within the SNr with the cortex. In addition, local perfusion of buspirone increased GABA and glutamate release in the SNr of naive and 6-OHDA-lesioned rats but no effect in 6-OHDA/l-DOPA rats. In the 6-OHDA/l-DOPA group, increased 5-HT transporter and decreased 5-HT(1A)receptor expression was found. Conclusions and Implications The effects of buspirone in SNr are influenced by dopamine loss andl-DOPA treatment. The present results suggest that the regulation of burst activity of the SNr induced by DA loss may be a good target to test new drugs for the treatment of PD and LID. | es_ES |
dc.description.sponsorship | Eusko Jaurlaritza, Grant/Award Numbers: IT747-13, T747-13; Ministerio de Economia y Competitividad, Grant/Award Number: SAF2016-77758-R | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-77758-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | DOPA-induced dyskinesia | es_ES |
dc.subject | abnormal involuntary movements | es_ES |
dc.subject | parkinsons-disease | es_ES |
dc.subject | dorsal raphe | es_ES |
dc.subject | substantia-nigra | es_ES |
dc.subject | nigrostriatal pathway | es_ES |
dc.subject | subthalamic nucleus | es_ES |
dc.subject | rat model | es_ES |
dc.subject | serotonergic dysfunction | es_ES |
dc.subject | 5-ht1a receptor stimulation | es_ES |
dc.title | 6-Hydroxydopamine lesion and levodopa treatment modif y the effect of buspirone in the substantia nigra pars reticulata | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15145 | es_ES |
dc.identifier.doi | 10.1111/bph.15145 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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Except where otherwise noted, this item's license is described as 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.