Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/4753 |
Resumo: | Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exposed to cocaine or amphetamine, as compared to H2O2 exposure. Chronic cocaine treatment induced sensitization to acute cocaine insult and increased cocaine-evoked accumulation of extracellular dopamine, although no changes in dihydroxyphenylacetic acid (DOPAC) levels were observed. Moreover, dopamine was depleted in cells chronically exposed to amphetamine and acute amphetamine toxicity persisted in these cells, indicating that dopamine was not involved in amphetamine cytotoxicity. PC12 cells chronically treated with H2O2 were totally resistant to acute H2O2, but not to acute cocaine or amphetamine exposure, suggesting that the toxicity induced by these stimulant drugs is unrelated to adaptation to oxidative stress. Interestingly, chronic cocaine treatment largely, but not completely, protected the cells against a H2O2 challenge, whilst a decrement in intracellular ATP was observed. This study shows that chronic treatment of PC12 cells with cocaine or H2O2 modifies the cytotoxic response to an acute exposure to these agents. |
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Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxideAmphetamineCocaineDrug abuseNeurotoxicityOxidative stressRepeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exposed to cocaine or amphetamine, as compared to H2O2 exposure. Chronic cocaine treatment induced sensitization to acute cocaine insult and increased cocaine-evoked accumulation of extracellular dopamine, although no changes in dihydroxyphenylacetic acid (DOPAC) levels were observed. Moreover, dopamine was depleted in cells chronically exposed to amphetamine and acute amphetamine toxicity persisted in these cells, indicating that dopamine was not involved in amphetamine cytotoxicity. PC12 cells chronically treated with H2O2 were totally resistant to acute H2O2, but not to acute cocaine or amphetamine exposure, suggesting that the toxicity induced by these stimulant drugs is unrelated to adaptation to oxidative stress. Interestingly, chronic cocaine treatment largely, but not completely, protected the cells against a H2O2 challenge, whilst a decrement in intracellular ATP was observed. This study shows that chronic treatment of PC12 cells with cocaine or H2O2 modifies the cytotoxic response to an acute exposure to these agents.http://www.sciencedirect.com/science/article/B6TCN-4HC6M2T-2/1/c10d106720c0286d647497caf01a3ae02006info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/4753http://hdl.handle.net/10316/4753engToxicology. 217:1 (2006) 54-62Cunha-Oliveira, TeresaRego, A. CristinaMorgadinho, Maria TeresaMacedo, TiceOliveira, Catarina Resendeinfo: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:RCAAP2021-09-30T09:24:10Zoai:estudogeral.uc.pt:10316/4753Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:43:27.172557Repositório 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 |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
title |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
spellingShingle |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide Cunha-Oliveira, Teresa Amphetamine Cocaine Drug abuse Neurotoxicity Oxidative stress |
title_short |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
title_full |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
title_fullStr |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
title_full_unstemmed |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
title_sort |
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide |
author |
Cunha-Oliveira, Teresa |
author_facet |
Cunha-Oliveira, Teresa Rego, A. Cristina Morgadinho, Maria Teresa Macedo, Tice Oliveira, Catarina Resende |
author_role |
author |
author2 |
Rego, A. Cristina Morgadinho, Maria Teresa Macedo, Tice Oliveira, Catarina Resende |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Cunha-Oliveira, Teresa Rego, A. Cristina Morgadinho, Maria Teresa Macedo, Tice Oliveira, Catarina Resende |
dc.subject.por.fl_str_mv |
Amphetamine Cocaine Drug abuse Neurotoxicity Oxidative stress |
topic |
Amphetamine Cocaine Drug abuse Neurotoxicity Oxidative stress |
description |
Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exposed to cocaine or amphetamine, as compared to H2O2 exposure. Chronic cocaine treatment induced sensitization to acute cocaine insult and increased cocaine-evoked accumulation of extracellular dopamine, although no changes in dihydroxyphenylacetic acid (DOPAC) levels were observed. Moreover, dopamine was depleted in cells chronically exposed to amphetamine and acute amphetamine toxicity persisted in these cells, indicating that dopamine was not involved in amphetamine cytotoxicity. PC12 cells chronically treated with H2O2 were totally resistant to acute H2O2, but not to acute cocaine or amphetamine exposure, suggesting that the toxicity induced by these stimulant drugs is unrelated to adaptation to oxidative stress. Interestingly, chronic cocaine treatment largely, but not completely, protected the cells against a H2O2 challenge, whilst a decrement in intracellular ATP was observed. This study shows that chronic treatment of PC12 cells with cocaine or H2O2 modifies the cytotoxic response to an acute exposure to these agents. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006 |
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/10316/4753 http://hdl.handle.net/10316/4753 |
url |
http://hdl.handle.net/10316/4753 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Toxicology. 217:1 (2006) 54-62 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133706621812736 |