Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas
Autor(a) principal: | |
---|---|
Data de Publicação: | 2011 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/4434 |
Resumo: | Repeated stress or stressful events has been reported to induce anxiety and depression. Differential responses to repeated stress and antidepressant treatments have been observed in males and females. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and limbic-hypothalamic-pituitary-adrenal (LHHA) axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. Thus, this study investigated sexrelated differential response to repeated restraint stress and chronic administration of clomipramine on parameters of oxidative stress in cerebral cortex, hippocampus and striatum (Manuscript 1) and behavior in rats (Manuscript 1). Male and female rats were divided into control and repeated restraint stress, and subdivided into treated or not with clomipramine during 40 days of stress and 27 days of clomipramine treatment (30mg/kg). The model of repeated restraint stress used in this study increased oxidative damage particularly in striatum and hippocampus of females in higher sensitivity to stress compared to males (Manuscript 1). In this context, the levels of non-enzymatic antioxidant such as the levels of non-protein thiol (NP-SH), and enzymatic antioxidants such as the enzyme superoxide dismutase (SOD), catalase (CAT) and Na+/ K+-ATPase (Manuscript 1) also changed in both sexes. Antidepressant treatment with clomipramine increased the oxidative damage caused by the imbalance between oxidants/antioxidants, particularly in males. Regarding the behavioral activities (Manuscript 1), females subjected to repeated restraint stress had higher anxiety and lower motivation when compared to males. On the other hand, males had impaired non-spatial memory formation through variables such as the short and long term memory as well as a reduction in exploratory and locomotor activity compared to females. Sex differences were also checked as to which antidepressant treatment that potentiate the deficits on the non-spatial memory formation, locomotor and exploratory activities and motivation in males, but in contrast was observed an increase in anxiety and a reduction on the consumption of sweet food in females. Finally, the results of this study indicate that females are particularly sensitive to stress on anxiety and motivation while males on the spatial memory formation as well as locomotor and exploratory acitvities. Antidepressant treatment with clomipramine appears to have neuroprotective effect in females, but cytotoxic in males in what might be observed by the increase in the neurochemical and behavioral deficits. |
id |
UFSM_7248114b7d778d36b669825f7c584202 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/4434 |
network_acronym_str |
UFSM |
network_name_str |
Manancial - Repositório Digital da UFSM |
repository_id_str |
|
spelling |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeasInteraction between repeated stress and clomipramine: diference response in male and female ratsEstresse repetido por contençãoClomipraminaEstresse oxidativoComportamentoRepeated restraint stressClomipramineOxidative stressBehaviorCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICARepeated stress or stressful events has been reported to induce anxiety and depression. Differential responses to repeated stress and antidepressant treatments have been observed in males and females. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and limbic-hypothalamic-pituitary-adrenal (LHHA) axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. Thus, this study investigated sexrelated differential response to repeated restraint stress and chronic administration of clomipramine on parameters of oxidative stress in cerebral cortex, hippocampus and striatum (Manuscript 1) and behavior in rats (Manuscript 1). Male and female rats were divided into control and repeated restraint stress, and subdivided into treated or not with clomipramine during 40 days of stress and 27 days of clomipramine treatment (30mg/kg). The model of repeated restraint stress used in this study increased oxidative damage particularly in striatum and hippocampus of females in higher sensitivity to stress compared to males (Manuscript 1). In this context, the levels of non-enzymatic antioxidant such as the levels of non-protein thiol (NP-SH), and enzymatic antioxidants such as the enzyme superoxide dismutase (SOD), catalase (CAT) and Na+/ K+-ATPase (Manuscript 1) also changed in both sexes. Antidepressant treatment with clomipramine increased the oxidative damage caused by the imbalance between oxidants/antioxidants, particularly in males. Regarding the behavioral activities (Manuscript 1), females subjected to repeated restraint stress had higher anxiety and lower motivation when compared to males. On the other hand, males had impaired non-spatial memory formation through variables such as the short and long term memory as well as a reduction in exploratory and locomotor activity compared to females. Sex differences were also checked as to which antidepressant treatment that potentiate the deficits on the non-spatial memory formation, locomotor and exploratory activities and motivation in males, but in contrast was observed an increase in anxiety and a reduction on the consumption of sweet food in females. Finally, the results of this study indicate that females are particularly sensitive to stress on anxiety and motivation while males on the spatial memory formation as well as locomotor and exploratory acitvities. Antidepressant treatment with clomipramine appears to have neuroprotective effect in females, but cytotoxic in males in what might be observed by the increase in the neurochemical and behavioral deficits.O estresse pode ser definido como uma variedade de estímulos fisiológicos e psicológicos que podem ter efeitos diretos ou indiretos sobre a função corporal. Neste contexto o estresse repetido ou situações estressantes podem induzir ansiedade e depressão. Diferentes respostas quanto ao estresse repetido e tratamento antidepressivo são observadas em machos e fêmeas. A clomipramina é um antidepressivo tricíclico que inibe a recaptação de serotonina e norepinefrina com ações indiretas sobre o sistema dopaminérgico e eixo límbico-hipotálamo-hipófise-adrenal (LHHA). Seu uso crônico aumenta a habilidade do corpo em combater o estresse, contudo doses elevadas podem potencializar os efeitos colaterais sobre memória, aprendizado e função sensório-motora. Desta forma, este estudo investigou as diferenças sexuais quanto ao estresse repetido por contenção e tratamento crônico com clomipramina sobre parâmetros de estresse oxidativo em córtex cerebral, estriado e hipocampo (Artigo 1 e Manuscrito 1) e comportamento de ratos (Artigo 2 e Manuscrito 1). Machos e fêmeas foram divididos em controle e estresse e subdivididos em tratados ou não com clomipramina durante 40 dias de estresse e 27 dias consecutivos de tratamento com clomipramina (30mg/kg). O modelo de estresse repetido por contenção utilizado neste estudo aumentou o dano oxidativo particularmente em estriado e hipocampo de fêmeas determinando maior sensibilidade ao estresse em comparação aos machos (Manuscrito 1). Neste contexto os níveis antioxidantes não-enzimáticos como tióis nãoprotéicos (NP-SH), enzimáticos tais como a enzima superóxido dismutase (SOD) e catalase (CAT) e Na+/ K+-ATPase (Manuscrito 1) também sofreram alterações em ambos os sexos. O tratamento antidepressivo com clomipramina potencializou o dano oxidativo causado pelo desequilíbrio entre oxidantes/antioxidantes, particularmente em machos. Em relação às atividades comportamentais (Manuscrito 1) fêmeas submetidas à estresse repetido por contenção apresentaram maior ansiedade e menor motivação quando comparado aos machos. Por outro lado, machos apresentaram prejuízo na formação de memória não espacial através das variáveis de memória em curto e longo prazo assim como uma redução na atividade locomotora e exploratória em relação ás fêmeas. Diferenças sexuais foram verificadas também quanto ao tratamento antidepressivo o qual potencializou os déficits sobre a formação da memória não espacial e atividade locomotora e exploratória assim como motivação em machos, mas em contrapartida foi observado um aumento da ansiedade e uma redução quanto ao consumo de alimento doce em fêmeas. Por fim, os resultados deste estudo indicam que fêmeas são sensíveis ao estresse particularmente sobre ansiedade e motivação enquanto machos são sensíveis à formação de memória não espacial assim como atividade locomotora e exploratória. O tratamento antidepressivo com clomipramina na dose utilizada parece ter efeito neuroprotetor em fêmeas, mas citotóxico em machos o que pôde ser observado pelo aumento nos déficits neuroquímicos e comportamentais.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaSoares, Félix Alexandre Antuneshttp://lattes.cnpq.br/8752453650114092Furian, Ana Fláviahttp://lattes.cnpq.br/0865191340133424Savegnago, Luciellihttp://lattes.cnpq.br/1480751214999787Royes, Luiz Fernando Freirehttp://lattes.cnpq.br/0543081555633400Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Balk, Rodrigo de Souza2017-04-262017-04-262011-10-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfBALK, Rodrigo de Souza. Interaction between repeated stress and clomipramine: diference response in male and female rats. 2011. 110 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011.http://repositorio.ufsm.br/handle/1/4434porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2023-05-23T12:25:42Zoai:repositorio.ufsm.br:1/4434Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-05-23T12:25:42Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas Interaction between repeated stress and clomipramine: diference response in male and female rats |
title |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas |
spellingShingle |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas Balk, Rodrigo de Souza Estresse repetido por contenção Clomipramina Estresse oxidativo Comportamento Repeated restraint stress Clomipramine Oxidative stress Behavior CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas |
title_full |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas |
title_fullStr |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas |
title_full_unstemmed |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas |
title_sort |
Interações entre o estresse repetido e clomipramina: diferentes respostas em ratos machos e fêmeas |
author |
Balk, Rodrigo de Souza |
author_facet |
Balk, Rodrigo de Souza |
author_role |
author |
dc.contributor.none.fl_str_mv |
Soares, Félix Alexandre Antunes http://lattes.cnpq.br/8752453650114092 Furian, Ana Flávia http://lattes.cnpq.br/0865191340133424 Savegnago, Lucielli http://lattes.cnpq.br/1480751214999787 Royes, Luiz Fernando Freire http://lattes.cnpq.br/0543081555633400 Fachinetto, Roselei http://lattes.cnpq.br/7203076675431306 |
dc.contributor.author.fl_str_mv |
Balk, Rodrigo de Souza |
dc.subject.por.fl_str_mv |
Estresse repetido por contenção Clomipramina Estresse oxidativo Comportamento Repeated restraint stress Clomipramine Oxidative stress Behavior CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Estresse repetido por contenção Clomipramina Estresse oxidativo Comportamento Repeated restraint stress Clomipramine Oxidative stress Behavior CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Repeated stress or stressful events has been reported to induce anxiety and depression. Differential responses to repeated stress and antidepressant treatments have been observed in males and females. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and limbic-hypothalamic-pituitary-adrenal (LHHA) axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. Thus, this study investigated sexrelated differential response to repeated restraint stress and chronic administration of clomipramine on parameters of oxidative stress in cerebral cortex, hippocampus and striatum (Manuscript 1) and behavior in rats (Manuscript 1). Male and female rats were divided into control and repeated restraint stress, and subdivided into treated or not with clomipramine during 40 days of stress and 27 days of clomipramine treatment (30mg/kg). The model of repeated restraint stress used in this study increased oxidative damage particularly in striatum and hippocampus of females in higher sensitivity to stress compared to males (Manuscript 1). In this context, the levels of non-enzymatic antioxidant such as the levels of non-protein thiol (NP-SH), and enzymatic antioxidants such as the enzyme superoxide dismutase (SOD), catalase (CAT) and Na+/ K+-ATPase (Manuscript 1) also changed in both sexes. Antidepressant treatment with clomipramine increased the oxidative damage caused by the imbalance between oxidants/antioxidants, particularly in males. Regarding the behavioral activities (Manuscript 1), females subjected to repeated restraint stress had higher anxiety and lower motivation when compared to males. On the other hand, males had impaired non-spatial memory formation through variables such as the short and long term memory as well as a reduction in exploratory and locomotor activity compared to females. Sex differences were also checked as to which antidepressant treatment that potentiate the deficits on the non-spatial memory formation, locomotor and exploratory activities and motivation in males, but in contrast was observed an increase in anxiety and a reduction on the consumption of sweet food in females. Finally, the results of this study indicate that females are particularly sensitive to stress on anxiety and motivation while males on the spatial memory formation as well as locomotor and exploratory acitvities. Antidepressant treatment with clomipramine appears to have neuroprotective effect in females, but cytotoxic in males in what might be observed by the increase in the neurochemical and behavioral deficits. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-10-14 2017-04-26 2017-04-26 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
BALK, Rodrigo de Souza. Interaction between repeated stress and clomipramine: diference response in male and female rats. 2011. 110 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011. http://repositorio.ufsm.br/handle/1/4434 |
identifier_str_mv |
BALK, Rodrigo de Souza. Interaction between repeated stress and clomipramine: diference response in male and female rats. 2011. 110 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011. |
url |
http://repositorio.ufsm.br/handle/1/4434 |
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 |
_version_ |
1805922141279879168 |