Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/11139 |
Resumo: | Depression is a serious, recurrent and incapacitating psychiatric condition with a heavy social burden. The pharmacological approach to this disorder employs therapy with antidepressant drugs, which have side effects and numerous limitations. In view of the promising pharmacological properties of containing-selenium molecules, this study evaluated the effect of 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene (DPS) in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of depressant activity. Since serotonin (5-HT) plays an important role in the pathophysiology of depressive disorders, the involvement of serotonergic system and 5-HT receptors in the action caused by DPS was studied. The antidepressant-like action of combined treatment with subeffective doses of both DPS plus paroxetine, a selective serotonin reuptake inhibitor (SSRI) was investigated. Further, we verified the possible mechanism responsible for antidepressant-like action of DPS. The results showed that DPS (50 and 100 mg/kg, p.o.) significantly reduced the immobility time during the FST and TST, without accompanying changes in ambulation when assessed in the open-field test. The anti-immobility effect of DPS (50 mg/kg, i.g.) in the FST was prevented by pretreatment of mice with pCPA (p-chlorophenylalanine; an inhibitor of 5-HT synthesis, 100 mg/kg, i.p., once a day for 4 consecutive days,), WAY 100635 (N-[2- [4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide; 0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist), ritanserin (1 mg/kg, i.p., a 5-HT2 receptor antagonist) or ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). Combined treatment with paroxetine and DPS reduced the immobility time in the FST. DPS at the dose of 50 mg/kg did not produce any change in the cerebral activity of monoamine oxidase subtypes (MAO-A or MAO-B). DPS at the dose of 50 mg/kg inhibited significantly 5-HT uptake in mouse brain synaptosomes. These results suggest that DPS produced an antidepressant-like action in the mouse FST and TST and this action seems most likely to be mediated through an interaction with serotonergic system, particularly by 5-HT reuptake inhibition. |
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Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgicoAntidepressant-like pharmacological profile of 3-(4- Fluorophenylselenyl)-2,5-diphenylselenophene: involvement of serotonergic systemCompostos orgânicos de selênioSelenofenosTipo antidepressivoSistema serotoninérgicoTeste do nado forçadoTeste da suspensão da caudaOrganoselenium compoundsSelenopheneAntidepressant-likeSerotonergic systemForced swimming testTail suspension testCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICADepression is a serious, recurrent and incapacitating psychiatric condition with a heavy social burden. The pharmacological approach to this disorder employs therapy with antidepressant drugs, which have side effects and numerous limitations. In view of the promising pharmacological properties of containing-selenium molecules, this study evaluated the effect of 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene (DPS) in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of depressant activity. Since serotonin (5-HT) plays an important role in the pathophysiology of depressive disorders, the involvement of serotonergic system and 5-HT receptors in the action caused by DPS was studied. The antidepressant-like action of combined treatment with subeffective doses of both DPS plus paroxetine, a selective serotonin reuptake inhibitor (SSRI) was investigated. Further, we verified the possible mechanism responsible for antidepressant-like action of DPS. The results showed that DPS (50 and 100 mg/kg, p.o.) significantly reduced the immobility time during the FST and TST, without accompanying changes in ambulation when assessed in the open-field test. The anti-immobility effect of DPS (50 mg/kg, i.g.) in the FST was prevented by pretreatment of mice with pCPA (p-chlorophenylalanine; an inhibitor of 5-HT synthesis, 100 mg/kg, i.p., once a day for 4 consecutive days,), WAY 100635 (N-[2- [4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide; 0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist), ritanserin (1 mg/kg, i.p., a 5-HT2 receptor antagonist) or ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). Combined treatment with paroxetine and DPS reduced the immobility time in the FST. DPS at the dose of 50 mg/kg did not produce any change in the cerebral activity of monoamine oxidase subtypes (MAO-A or MAO-B). DPS at the dose of 50 mg/kg inhibited significantly 5-HT uptake in mouse brain synaptosomes. These results suggest that DPS produced an antidepressant-like action in the mouse FST and TST and this action seems most likely to be mediated through an interaction with serotonergic system, particularly by 5-HT reuptake inhibition.Conselho Nacional de Desenvolvimento Científico e TecnológicoA depressão é uma doença grave, recorrente e uma condição psiquiátrica incapacitante que gera pesados custos sociais. A abordagem farmacológica dessa desordem é feita por meio do emprego de antidepressivos, os quais apresentam efeitos adversos e numerosas limitações. Tendo em vista as promissoras propriedades farmacológicas das moléculas contendo selênio, este estudo avaliou o efeito do 3-(4-fluorofenilselenil)-2,5-difenilselenofeno (DPS) no teste do nado forçado (TNF) e no teste da suspensão da cauda (TSC) em camundongos, dois modelos preditivos de comportamento depressivo. Uma vez que a serotonina (5-HT) desempenha um importante papel na patofisiologia dos transtornos depressivos, o envolvimento do sistema serotoninérgico e dos receptores de 5-HT na ação desenvolvida pelo DPS foi estudado. A ação do tipo antidepressiva do tratamento combinado com doses subefetivas de DPS e paroxetina, um inibidor seletivo da recaptação de serotonina (ISRS) foi investigada. Além disso, o possível mecanismo responsável pela ação do tipo antidepressiva do DPS também foi verificado. Os resultados mostram que o DPS (50 e 100 mg/kg) reduziu significativamente o tempo de imobilidade durante os TSC e TNF, sem causar alterações na atividade locomotora no teste do campo aberto (TCA). O efeito anti-imobilidade do DPS (50 mg/kg, i.g.) no TNF foi prevenido pelo pré-tratamento dos animais com pCPA (p-clorofenilalanina; 100 mg/kg, i.p., administrado uma vez ao dia durante 4 dias consecutivos, um inibidor da síntese de serotonina), WAY 100635 (N-[2-[4-(2-metoxifenil)-1-piperazinil]etil]-N-2- piridinilciclohexano carboxamida; 0,1 mg/kg, s.c., um antagonista seletivo de receptores 5- HT1A), ritanserina (1 mg/kg, i.p., um antagonista seletivo de receptores 5-HT2) ou ondansetrona (1 mg/kg, i.p., um antagonista seletivo de receptores 5-HT3). O tratamento combinado com paroxetina e DPS reduziu o tempo de imobilidade no TNF. O DPS na dose de 50 mg/kg não produziu nenhuma alteração na atividade dos subtipos da monoamino oxidase (MAO-A e MAO-B) cerebral. O DPS na dose de 50 mg/kg inibiu significantemente a captação de 5-HT em sinaptossoma de cérebro de camundongos. Esses resultados sugerem que o DPS produziu uma ação do tipo antidepressiva no TSC e no TNF em camundongos e esta ação parece ser mediada por uma interação com o sistema serotoninérgico, particularmente por uma inibição da recaptação de 5-HT.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Burger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Athayde, Margareth Lindehttp://lattes.cnpq.br/7866111734540735Gai, Bibiana Mozzaquatro2017-04-202017-04-202011-02-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfGAI, Bibiana Mozzaquatro. Antidepressant-like pharmacological profile of 3-(4- Fluorophenylselenyl)-2,5-diphenylselenophene: involvement of serotonergic system. 2011. 90 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011.http://repositorio.ufsm.br/handle/1/11139porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-09-14T11:39:32Zoai:repositorio.ufsm.br:1/11139Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-09-14T11:39:32Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico Antidepressant-like pharmacological profile of 3-(4- Fluorophenylselenyl)-2,5-diphenylselenophene: involvement of serotonergic system |
title |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico |
spellingShingle |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico Gai, Bibiana Mozzaquatro Compostos orgânicos de selênio Selenofenos Tipo antidepressivo Sistema serotoninérgico Teste do nado forçado Teste da suspensão da cauda Organoselenium compounds Selenophene Antidepressant-like Serotonergic system Forced swimming test Tail suspension test CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico |
title_full |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico |
title_fullStr |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico |
title_full_unstemmed |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico |
title_sort |
Perfil farmacológico do tipo antidepressivo do composto 3-(4-fluorofenilselenil)-2,5 difenilselenofeno: envolvimento do sistema serotoninérgico |
author |
Gai, Bibiana Mozzaquatro |
author_facet |
Gai, Bibiana Mozzaquatro |
author_role |
author |
dc.contributor.none.fl_str_mv |
Nogueira, Cristina Wayne http://lattes.cnpq.br/2877042401245169 Burger, Marilise Escobar http://lattes.cnpq.br/9128090974948413 Athayde, Margareth Linde http://lattes.cnpq.br/7866111734540735 |
dc.contributor.author.fl_str_mv |
Gai, Bibiana Mozzaquatro |
dc.subject.por.fl_str_mv |
Compostos orgânicos de selênio Selenofenos Tipo antidepressivo Sistema serotoninérgico Teste do nado forçado Teste da suspensão da cauda Organoselenium compounds Selenophene Antidepressant-like Serotonergic system Forced swimming test Tail suspension test CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Compostos orgânicos de selênio Selenofenos Tipo antidepressivo Sistema serotoninérgico Teste do nado forçado Teste da suspensão da cauda Organoselenium compounds Selenophene Antidepressant-like Serotonergic system Forced swimming test Tail suspension test CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Depression is a serious, recurrent and incapacitating psychiatric condition with a heavy social burden. The pharmacological approach to this disorder employs therapy with antidepressant drugs, which have side effects and numerous limitations. In view of the promising pharmacological properties of containing-selenium molecules, this study evaluated the effect of 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene (DPS) in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of depressant activity. Since serotonin (5-HT) plays an important role in the pathophysiology of depressive disorders, the involvement of serotonergic system and 5-HT receptors in the action caused by DPS was studied. The antidepressant-like action of combined treatment with subeffective doses of both DPS plus paroxetine, a selective serotonin reuptake inhibitor (SSRI) was investigated. Further, we verified the possible mechanism responsible for antidepressant-like action of DPS. The results showed that DPS (50 and 100 mg/kg, p.o.) significantly reduced the immobility time during the FST and TST, without accompanying changes in ambulation when assessed in the open-field test. The anti-immobility effect of DPS (50 mg/kg, i.g.) in the FST was prevented by pretreatment of mice with pCPA (p-chlorophenylalanine; an inhibitor of 5-HT synthesis, 100 mg/kg, i.p., once a day for 4 consecutive days,), WAY 100635 (N-[2- [4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide; 0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist), ritanserin (1 mg/kg, i.p., a 5-HT2 receptor antagonist) or ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). Combined treatment with paroxetine and DPS reduced the immobility time in the FST. DPS at the dose of 50 mg/kg did not produce any change in the cerebral activity of monoamine oxidase subtypes (MAO-A or MAO-B). DPS at the dose of 50 mg/kg inhibited significantly 5-HT uptake in mouse brain synaptosomes. These results suggest that DPS produced an antidepressant-like action in the mouse FST and TST and this action seems most likely to be mediated through an interaction with serotonergic system, particularly by 5-HT reuptake inhibition. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-02-23 2017-04-20 2017-04-20 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
GAI, Bibiana Mozzaquatro. Antidepressant-like pharmacological profile of 3-(4- Fluorophenylselenyl)-2,5-diphenylselenophene: involvement of serotonergic system. 2011. 90 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011. http://repositorio.ufsm.br/handle/1/11139 |
identifier_str_mv |
GAI, Bibiana Mozzaquatro. Antidepressant-like pharmacological profile of 3-(4- Fluorophenylselenyl)-2,5-diphenylselenophene: involvement of serotonergic system. 2011. 90 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011. |
url |
http://repositorio.ufsm.br/handle/1/11139 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922077685841920 |