Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease

Detalhes bibliográficos
Autor(a) principal: Carvalho, Miguel M.
Data de Publicação: 2017
Outros Autores: Campos, Filipa L., Marques, Mariana, Cunha, Carina Isabel Soares, Kokras, Nikolaos, Dalla, Christina, Leite-Almeida, Hugo, Sousa, Nuno, Salgado, A. J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/49727
Resumo: The use of dopamine replacement therapies (DRT) in the treatment of Parkinson's disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD.
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spelling Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's DiseaseParkinson’s diseaseDopamine dysregulation syndromeImpulse control disorders6-OHDALevodopaCiências Médicas::Medicina BásicaScience & TechnologyThe use of dopamine replacement therapies (DRT) in the treatment of Parkinson's disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD.Portuguese Foundation for Science and Technology: Ciência 2007 Program and IF Development Grant (IF/00111/2013) to AJS, Portuguese Foundation for Science and Technology PhD scholarships attributed to MMC (SFRH/BD/51061/2010), FLC (SFRH/BD/47311/2008) and CS-C (SFRH/BD/51992/2012), and Post-Doctoral Fellowship to HL-A (SFRH/BPD/80118/2011). Neurochemical analysis was funded from ELKE/UOA: 11650. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersionFrontiers MediaUniversidade do MinhoCarvalho, Miguel M.Campos, Filipa L.Marques, MarianaCunha, Carina Isabel SoaresKokras, NikolaosDalla, ChristinaLeite-Almeida, HugoSousa, NunoSalgado, A. J.20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/49727engCarvalho, M. M., Campos, F. L., Marques, M., Soares-Cunha, C., Kokras, N., Dalla, C., ... & Salgado, A. J. (2017). Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson’s Disease. Frontiers in behavioral neuroscience, 11, 1451662-515310.3389/fnbeh.2017.00145https://www.frontiersin.org/articles/10.3389/fnbeh.2017.00145/fullinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:03:55Zoai:repositorium.sdum.uminho.pt:1822/49727Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:54:06.085946Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
title Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
spellingShingle Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
Carvalho, Miguel M.
Parkinson’s disease
Dopamine dysregulation syndrome
Impulse control disorders
6-OHDA
Levodopa
Ciências Médicas::Medicina Básica
Science & Technology
title_short Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
title_full Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
title_fullStr Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
title_full_unstemmed Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
title_sort Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease
author Carvalho, Miguel M.
author_facet Carvalho, Miguel M.
Campos, Filipa L.
Marques, Mariana
Cunha, Carina Isabel Soares
Kokras, Nikolaos
Dalla, Christina
Leite-Almeida, Hugo
Sousa, Nuno
Salgado, A. J.
author_role author
author2 Campos, Filipa L.
Marques, Mariana
Cunha, Carina Isabel Soares
Kokras, Nikolaos
Dalla, Christina
Leite-Almeida, Hugo
Sousa, Nuno
Salgado, A. J.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Carvalho, Miguel M.
Campos, Filipa L.
Marques, Mariana
Cunha, Carina Isabel Soares
Kokras, Nikolaos
Dalla, Christina
Leite-Almeida, Hugo
Sousa, Nuno
Salgado, A. J.
dc.subject.por.fl_str_mv Parkinson’s disease
Dopamine dysregulation syndrome
Impulse control disorders
6-OHDA
Levodopa
Ciências Médicas::Medicina Básica
Science & Technology
topic Parkinson’s disease
Dopamine dysregulation syndrome
Impulse control disorders
6-OHDA
Levodopa
Ciências Médicas::Medicina Básica
Science & Technology
description The use of dopamine replacement therapies (DRT) in the treatment of Parkinson's disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/49727
url http://hdl.handle.net/1822/49727
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Carvalho, M. M., Campos, F. L., Marques, M., Soares-Cunha, C., Kokras, N., Dalla, C., ... & Salgado, A. J. (2017). Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson’s Disease. Frontiers in behavioral neuroscience, 11, 145
1662-5153
10.3389/fnbeh.2017.00145
https://www.frontiersin.org/articles/10.3389/fnbeh.2017.00145/full
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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