Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes
Coadministration of entacapone with levodopa attenuates motor complications in experimental models of Parkinson's disease. The mechanisms underlying entacapone effects are unknown. We investigated the effect of entacapone, on: long-duration response (LDR) to levodopa, levodopa-induced postsynap...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996108001721 |
| _version_ | 1818734907050950656 |
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| author | C. Marin E. Aguilar G. Mengod R. Cortés M.C. Rodríguez-Oroz J.A. Obeso |
| author_facet | C. Marin E. Aguilar G. Mengod R. Cortés M.C. Rodríguez-Oroz J.A. Obeso |
| author_sort | C. Marin |
| collection | DOAJ |
| description | Coadministration of entacapone with levodopa attenuates motor complications in experimental models of Parkinson's disease. The mechanisms underlying entacapone effects are unknown. We investigated the effect of entacapone, on: long-duration response (LDR) to levodopa, levodopa-induced postsynaptic pharmacodynamic mechanisms and molecular changes in hemiparkinsonian rats. 6-Hydroxydopamine-unilaterally lesioned rats were treated with levodopa (25 mg/kg)+vehicle; levodopa+entacapone (30 mg/kg) or saline, twice daily for 22 days. The LDR and the apomorphine-induced rotations were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin and dopamine D-3 receptor mRNAs, subthalamic cytochrome oxidase mRNA and nigral glutamic acid decarboxylase mRNA. Entacapone potentiated the LDR but did not modify either the apomorphine-induced rotational behavior or the molecular changes. Our results suggest that the effects of entacapone on levodopa-induced motor response are not mediated by postsynaptic mechanisms and that administration of entacapone is not able to normalize the molecular alterations induced by levodopa in the basal ganglia. |
| first_indexed | 2024-12-18T00:12:49Z |
| format | Article |
| id | doaj.art-7c1c8eab79cf4790b9dbdf319e1ce139 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-18T00:12:49Z |
| publishDate | 2008-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-7c1c8eab79cf4790b9dbdf319e1ce1392022-12-21T21:27:38ZengElsevierNeurobiology of Disease1095-953X2008-12-01323340348Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changesC. Marin0E. Aguilar1G. Mengod2R. Cortés3M.C. Rodríguez-Oroz4J.A. Obeso5Laboratori de Neurologia Experimental, Àrea de Neurociències, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), Spain; Corresponding author. Laboratori de Neurologia, Servei de Neurologia, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Fax: +34 93 2275783.Laboratori de Neurologia Experimental, Àrea de Neurociències, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainDepartament de Neuroquímica i Neurofarmacologia, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Barcelona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), SpainDepartament de Neuroquímica i Neurofarmacologia, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Barcelona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), SpainDepartment of Neurology and Neurosurgery, Neuroscience Center, Clínica Universitaria and Medical School, University of Navarra and CIMA, Pamplona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), SpainDepartment of Neurology and Neurosurgery, Neuroscience Center, Clínica Universitaria and Medical School, University of Navarra and CIMA, Pamplona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), SpainCoadministration of entacapone with levodopa attenuates motor complications in experimental models of Parkinson's disease. The mechanisms underlying entacapone effects are unknown. We investigated the effect of entacapone, on: long-duration response (LDR) to levodopa, levodopa-induced postsynaptic pharmacodynamic mechanisms and molecular changes in hemiparkinsonian rats. 6-Hydroxydopamine-unilaterally lesioned rats were treated with levodopa (25 mg/kg)+vehicle; levodopa+entacapone (30 mg/kg) or saline, twice daily for 22 days. The LDR and the apomorphine-induced rotations were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin and dopamine D-3 receptor mRNAs, subthalamic cytochrome oxidase mRNA and nigral glutamic acid decarboxylase mRNA. Entacapone potentiated the LDR but did not modify either the apomorphine-induced rotational behavior or the molecular changes. Our results suggest that the effects of entacapone on levodopa-induced motor response are not mediated by postsynaptic mechanisms and that administration of entacapone is not able to normalize the molecular alterations induced by levodopa in the basal ganglia.http://www.sciencedirect.com/science/article/pii/S0969996108001721Parkinson's diseaseLevodopaEntacapone6-HydroxydopaminePreproenkephalinPreprodynorphin |
| spellingShingle | C. Marin E. Aguilar G. Mengod R. Cortés M.C. Rodríguez-Oroz J.A. Obeso Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes Neurobiology of Disease Parkinson's disease Levodopa Entacapone 6-Hydroxydopamine Preproenkephalin Preprodynorphin |
| title | Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes |
| title_full | Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes |
| title_fullStr | Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes |
| title_full_unstemmed | Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes |
| title_short | Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes |
| title_sort | entacapone potentiates the long duration response but does not normalize levodopa induced molecular changes |
| topic | Parkinson's disease Levodopa Entacapone 6-Hydroxydopamine Preproenkephalin Preprodynorphin |
| url | http://www.sciencedirect.com/science/article/pii/S0969996108001721 |
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