Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18052 |
Resumo: | Schizophrenia is a psychiatric disorder that affects about 1% population around the world and its pharmacological treatment consist in the use of antipsychotics. Haloperidol, a first generation antipsychotic (FGA) acts primarily by blocking dopamine D2 receptors, while risperidone, a second generation antipsychotic (SGA), also acts through antagonism of serotonin receptors 5-HT2A serotonin receptor. Among the side effects related to the use of these drugs are the motor disorders, which are more related to the use of SGA. Tardive dyskinesia (TD), a behavioral disorder associated with chronic antipsychotic treatment, is characterized by involuntary movements, predominantly on the orofacial region, and its pathophysiology is not well understood. This study aimed to evaluate behavioral, inflammatory and dopaminergic changes in rats treated with haloperidol (1.0 mg/kg/day) or risperidone (2 mg/kg/day) for 28 days. There was a significant increase on vacuous chewing movements (VCM) in rats treated with haloperidol, but not risperidone, as well as a decrease in locomotor and exploratory activity. Both antipsychotic increased the levels of pro-inflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], tumor necrosis factor-α [TNF- α] and γ interferon [IFN-γ]) and decreased the anti-inflammatory (interleukin-10 [IL-10]) in the striatum. Correlation analysis showed a positive relation between increased number of VCM and IL-1β and INF-γ levels. Oxidative and antioxidant markers (levels of thiobarbituric acid reactive substances [TBARS], catalase and protein and nonprotein thiols) showed no significant changes in the cortex of rats treated with both antipsychotics. The activity of the enzyme monoamine oxidase (MAO-A and MAO-B) in the cerebral cortex, in rats treated with haloperidol or risperidone remained in the control group levels and the immunoreactivity of the enzyme tyrosine hydroxylase (TH) and dopamine transporter (DAT), showed no significant difference when evaluated also in the cortex of animals treated with both antipsychotics. Analyzing together, the results suggest that elevated levels of inflammatory markers can be linked to the development of DT. However, these results should be treated with reserve, once the risperidone-treated group also showed a change in cytokine levels. Also, suggest that treatment with haloperidol or risperidone does not change the parameters dopaminergic and does not cause oxidative damage in the cerebral cortex, suggesting that the cortex may not be related to the development of motor disorder. |
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2019-08-28T13:10:16Z2019-08-28T13:10:16Z2016-08-29http://repositorio.ufsm.br/handle/1/18052Schizophrenia is a psychiatric disorder that affects about 1% population around the world and its pharmacological treatment consist in the use of antipsychotics. Haloperidol, a first generation antipsychotic (FGA) acts primarily by blocking dopamine D2 receptors, while risperidone, a second generation antipsychotic (SGA), also acts through antagonism of serotonin receptors 5-HT2A serotonin receptor. Among the side effects related to the use of these drugs are the motor disorders, which are more related to the use of SGA. Tardive dyskinesia (TD), a behavioral disorder associated with chronic antipsychotic treatment, is characterized by involuntary movements, predominantly on the orofacial region, and its pathophysiology is not well understood. This study aimed to evaluate behavioral, inflammatory and dopaminergic changes in rats treated with haloperidol (1.0 mg/kg/day) or risperidone (2 mg/kg/day) for 28 days. There was a significant increase on vacuous chewing movements (VCM) in rats treated with haloperidol, but not risperidone, as well as a decrease in locomotor and exploratory activity. Both antipsychotic increased the levels of pro-inflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], tumor necrosis factor-α [TNF- α] and γ interferon [IFN-γ]) and decreased the anti-inflammatory (interleukin-10 [IL-10]) in the striatum. Correlation analysis showed a positive relation between increased number of VCM and IL-1β and INF-γ levels. Oxidative and antioxidant markers (levels of thiobarbituric acid reactive substances [TBARS], catalase and protein and nonprotein thiols) showed no significant changes in the cortex of rats treated with both antipsychotics. The activity of the enzyme monoamine oxidase (MAO-A and MAO-B) in the cerebral cortex, in rats treated with haloperidol or risperidone remained in the control group levels and the immunoreactivity of the enzyme tyrosine hydroxylase (TH) and dopamine transporter (DAT), showed no significant difference when evaluated also in the cortex of animals treated with both antipsychotics. Analyzing together, the results suggest that elevated levels of inflammatory markers can be linked to the development of DT. However, these results should be treated with reserve, once the risperidone-treated group also showed a change in cytokine levels. Also, suggest that treatment with haloperidol or risperidone does not change the parameters dopaminergic and does not cause oxidative damage in the cerebral cortex, suggesting that the cortex may not be related to the development of motor disorder.A esquizofrenia é uma doença psiquiátrica que atinge cerca de 1% da população mundial e seu tratamento farmacológico consiste na utilização de antipsicóticos. O haloperidol, um antipsicótico de primeira geração (APG) atua principalmente através do bloqueio dos receptores de dopamina D2, enquanto a risperidona, um antipsicótico de segunda geração (ASG), atua também através do antagonismo dos receptores de serotonina 5-HT2A. Dentre os efeitos colaterais relacionados ao uso desses fármacos estão os distúrbios motores, os quais estão mais relacionados ao uso de APG. A discinesia tardia (DT), uma alteração motora associada ao tratamento crônico com antipsicóticos, é caracterizada por movimentos involuntários, principalmente da região orofacial e sua fisiopatologia ainda não está bem elucidada. Este trabalho objetivou avaliar as alterações comportamentais, inflamatórias e dopaminérgicas em ratos tratados com haloperidol (1,0 mg/kg/dia) ou risperidona (2 mg/kg/dia) durante 28 dias. Houve um aumento significativo no número de movimentos de mascar no vazio (MMV) nos ratos tratados com haloperidol, mas não risperidona, além de uma redução na atividade locomotora e exploratória. Ambos os antipsicóticos aumentaram os níveis de citocinas pró-inflamatórias (interleucina-1β [IL-1β], interleucina-6 [IL-6], fator de necrose tumoral-α [TNF-α] e interferon- γ [IFN-γ]) e diminuíram a citocina antiinflamatória (interleucina-10 [IL-10]) no estriado. As análises de correlação mostraram uma relação significativa e positiva entre o aumento do número de MMV e os níveis de IL-1β e INF-γ. Os marcadores oxidativos e antioxidantes (níveis de substâncias reativas ao ácido tiobarbitúrico [TBARS], catalase e tióis proteico e não proteico) não mostraram qualquer alteração significativa no córtex de ratos tratados com ambos os antipsicóticos. A atividade da enzima monoaminoxidase (MAO-A e MAO-B) no córtex cerebral, para haloperidol e risperidona, manteve-se aos níveis do grupo controle e a imunorreatividade da enzima tirosina hidroxilase (TH) e do transportador de dopamina (TDA) não apresentou diferença significativa quando avaliada também no córtex de animais tratados com ambos os antipsicóticos. Analisando em conjunto, os resultados sugerem que elevados níveis de marcadores inflamatórios podem estar ligados ao desenvolvimento da DT. No entanto, esses resultados devem ser analisados com cautela, uma vez o grupo tratado com risperidona também apresentou alteração dos níveis de citocinas. Além disso, sugerem que o tratamento com haloperidol ou risperidona não altera os parâmetros dopaminérgicos nem acarreta dano oxidativo ao córtex cerebral, podendo essa estrutura cerebral não estar relacionada ao desenvolvimento dessa desordem motora.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessEsquizofreniaAntipsicóticosDiscinesia tardiaNeuroinflamaçãoCitocinasSchizophreniaAntipsychoticsTardive dyskinesiaNeuroinflammationCytokinesCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratosEffect of haloperidol or risperidone on behavioral, inflammatory and dopaminergic parameters in brain of ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisFachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Wagner, Carolinehttp://lattes.cnpq.br/4004565241849091Rosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Oliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175http://lattes.cnpq.br/5496934657690551Peroza, Luis Ricardo200800000002600e99bf03a-61e7-46c9-97d1-a7255476d47f183aef51-895d-4bfd-b59a-f165298a3f50580e04d6-2496-45ed-86a2-aa0657b902828ade1f91-8aa4-433a-8948-aa845c5ce69ddf67a9a8-bb2b-4fe4-b1ab-0baffdb61eadreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2016_PEROZA_LUIS.pdfTES_PPGCBBT_2016_PEROZA_LUIS.pdfTese de Doutoradoapplication/pdf3086681http://repositorio.ufsm.br/bitstream/1/18052/1/TES_PPGCBBT_2016_PEROZA_LUIS.pdfea1dee522a3986b9ae439ca87e8337beMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
dc.title.alternative.eng.fl_str_mv |
Effect of haloperidol or risperidone on behavioral, inflammatory and dopaminergic parameters in brain of rats |
title |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
spellingShingle |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos Peroza, Luis Ricardo Esquizofrenia Antipsicóticos Discinesia tardia Neuroinflamação Citocinas Schizophrenia Antipsychotics Tardive dyskinesia Neuroinflammation Cytokines CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
title_full |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
title_fullStr |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
title_full_unstemmed |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
title_sort |
Efeito do haloperidol ou risperidona sobre parâmetros comportamentais, inflamatórios e dopaminérgicos em cérebro de ratos |
author |
Peroza, Luis Ricardo |
author_facet |
Peroza, Luis Ricardo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7203076675431306 |
dc.contributor.referee1.fl_str_mv |
Wagner, Caroline |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4004565241849091 |
dc.contributor.referee2.fl_str_mv |
Rosemberg, Denis Broock |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7713953979203056 |
dc.contributor.referee3.fl_str_mv |
Oliveira, Mauro Schneider |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/7132934163734175 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5496934657690551 |
dc.contributor.author.fl_str_mv |
Peroza, Luis Ricardo |
contributor_str_mv |
Fachinetto, Roselei Wagner, Caroline Rosemberg, Denis Broock Oliveira, Mauro Schneider |
dc.subject.por.fl_str_mv |
Esquizofrenia Antipsicóticos Discinesia tardia Neuroinflamação Citocinas |
topic |
Esquizofrenia Antipsicóticos Discinesia tardia Neuroinflamação Citocinas Schizophrenia Antipsychotics Tardive dyskinesia Neuroinflammation Cytokines CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Schizophrenia Antipsychotics Tardive dyskinesia Neuroinflammation Cytokines |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Schizophrenia is a psychiatric disorder that affects about 1% population around the world and its pharmacological treatment consist in the use of antipsychotics. Haloperidol, a first generation antipsychotic (FGA) acts primarily by blocking dopamine D2 receptors, while risperidone, a second generation antipsychotic (SGA), also acts through antagonism of serotonin receptors 5-HT2A serotonin receptor. Among the side effects related to the use of these drugs are the motor disorders, which are more related to the use of SGA. Tardive dyskinesia (TD), a behavioral disorder associated with chronic antipsychotic treatment, is characterized by involuntary movements, predominantly on the orofacial region, and its pathophysiology is not well understood. This study aimed to evaluate behavioral, inflammatory and dopaminergic changes in rats treated with haloperidol (1.0 mg/kg/day) or risperidone (2 mg/kg/day) for 28 days. There was a significant increase on vacuous chewing movements (VCM) in rats treated with haloperidol, but not risperidone, as well as a decrease in locomotor and exploratory activity. Both antipsychotic increased the levels of pro-inflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], tumor necrosis factor-α [TNF- α] and γ interferon [IFN-γ]) and decreased the anti-inflammatory (interleukin-10 [IL-10]) in the striatum. Correlation analysis showed a positive relation between increased number of VCM and IL-1β and INF-γ levels. Oxidative and antioxidant markers (levels of thiobarbituric acid reactive substances [TBARS], catalase and protein and nonprotein thiols) showed no significant changes in the cortex of rats treated with both antipsychotics. The activity of the enzyme monoamine oxidase (MAO-A and MAO-B) in the cerebral cortex, in rats treated with haloperidol or risperidone remained in the control group levels and the immunoreactivity of the enzyme tyrosine hydroxylase (TH) and dopamine transporter (DAT), showed no significant difference when evaluated also in the cortex of animals treated with both antipsychotics. Analyzing together, the results suggest that elevated levels of inflammatory markers can be linked to the development of DT. However, these results should be treated with reserve, once the risperidone-treated group also showed a change in cytokine levels. Also, suggest that treatment with haloperidol or risperidone does not change the parameters dopaminergic and does not cause oxidative damage in the cerebral cortex, suggesting that the cortex may not be related to the development of motor disorder. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-08-29 |
dc.date.accessioned.fl_str_mv |
2019-08-28T13:10:16Z |
dc.date.available.fl_str_mv |
2019-08-28T13:10:16Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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http://repositorio.ufsm.br/handle/1/18052 |
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http://repositorio.ufsm.br/handle/1/18052 |
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por |
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por |
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200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
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