A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina
Ano de defesa: | 2016 |
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Autor(a) principal: | |
Outros Autores: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade do Estado do Rio de Janeiro
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Fisiopatologia Clínica e Experimental
|
Departamento: |
Centro Biomédico::Faculdade de Ciências Médicas
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://www.bdtd.uerj.br/handle/1/18251 |
Resumo: | Ketamine, a non-competitive NMDA receptor antagonist had its use restricted in human medicine because of its side effects attributed to subanesthetic doses. Currently, this drug is used as an experimental model of schizophrenia and also recreationally. Considering the contribution of behavioral sensitization to the study of antipsychotic effects and drug addiction, the present study was subdivided into 4 experiments. Experiment 1 (exp1) aimed to evaluate the development and expression of behavioral sensitization induced by subanesthetic doses (30 and 50 mg/kg) of ketamine. In experiments 2 and 3 (exp2 and exp3), the objectives were to investigate the role of the D2 and the 5-HT2 antagonists, raclopride and ketanserin, respectively. Finally, experiment 4 (exp4) aimed to evaluate the ability of ketamine to produce both conditioned and contextually sensitized locomotor responses. Initially, adult Swiss mice were submitted to 3 consecutive days of habituation in the open field for 60 (exp1) or 20 (exp2-3-4) minutes each day. After the habituation phase, each experiment followed its specific procedures. As for exp 1, seven consecutive days of exposure to 30 or 50 mg/kg ketamine demonstrated that 30 mg/kg produced the development of a sensitized locomotor response and, after 5 days of withdrawal, this same dose expressed a sensitized locomotor response. Based on these effects and on the lack of differences between males and females, for the next set of experiments we selected 30 mg/kg of ketamine to be administered in males. In exp2, 7 consecutive days of ketamine preceded by raclopride exposure indicated that the D2 blockade prevented both the development and expression of ketamine-induced behavioral sensitization, even in the absence of raclopride locomotor effects. Consistently, exp3 showed that the prevention of both responses occurred when ketamine was preceded by the 5-HT2 antagonist, ketanserin. Finally, in exp 4, the experimental protocol that included 7 consecutive days of injections unpaired and paired to the test environment demonstrated that ketamine paired to the open field produced a conditioned locomotor response following a challenge with saline, even after 2 days of ketamine withdrawal. In addition, it was shown that ketamine, when paired to the open field produced context-dependent behavioral sensitization. In summary, 30 mg/kg of ketamine developed and expressed a sensitized locomotor response, which was inhibited both by D2 and 5-HT2 antagonism. Interestingly the same dose interacted with environmental factors, resulting in a conditioned locomotor response and a context-dependent sensitization. Therefore, this study suggests a key role of both D2 and 5-HT2 receptors and the environmental context in the ketamine-induced behavioral sensitization. |
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Villaça, Yael de Abreuhttp://lattes.cnpq.br/2110538573461886Carrera, Marinete Pinheirohttp://lattes.cnpq.br/1314413290192367Pandolfo, Pablohttp://lattes.cnpq.br/8700964351768486Daltro-Santos, Penha Cristina Barradashttp://lattes.cnpq.br/9817163660114748Carvalho, Anderson Ribeirohttp://lattes.cnpq.br/9437798241357566http://lattes.cnpq.br/2070422598048012Costa, Jefferson Pires Galvanho dajfgalvanho@yahoo.com.br2022-08-22T16:21:10Z2016-02-29GALVANHO, Jefferson Pires. A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina. 2016. 107 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) – Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2016.http://www.bdtd.uerj.br/handle/1/18251Ketamine, a non-competitive NMDA receptor antagonist had its use restricted in human medicine because of its side effects attributed to subanesthetic doses. Currently, this drug is used as an experimental model of schizophrenia and also recreationally. Considering the contribution of behavioral sensitization to the study of antipsychotic effects and drug addiction, the present study was subdivided into 4 experiments. Experiment 1 (exp1) aimed to evaluate the development and expression of behavioral sensitization induced by subanesthetic doses (30 and 50 mg/kg) of ketamine. In experiments 2 and 3 (exp2 and exp3), the objectives were to investigate the role of the D2 and the 5-HT2 antagonists, raclopride and ketanserin, respectively. Finally, experiment 4 (exp4) aimed to evaluate the ability of ketamine to produce both conditioned and contextually sensitized locomotor responses. Initially, adult Swiss mice were submitted to 3 consecutive days of habituation in the open field for 60 (exp1) or 20 (exp2-3-4) minutes each day. After the habituation phase, each experiment followed its specific procedures. As for exp 1, seven consecutive days of exposure to 30 or 50 mg/kg ketamine demonstrated that 30 mg/kg produced the development of a sensitized locomotor response and, after 5 days of withdrawal, this same dose expressed a sensitized locomotor response. Based on these effects and on the lack of differences between males and females, for the next set of experiments we selected 30 mg/kg of ketamine to be administered in males. In exp2, 7 consecutive days of ketamine preceded by raclopride exposure indicated that the D2 blockade prevented both the development and expression of ketamine-induced behavioral sensitization, even in the absence of raclopride locomotor effects. Consistently, exp3 showed that the prevention of both responses occurred when ketamine was preceded by the 5-HT2 antagonist, ketanserin. Finally, in exp 4, the experimental protocol that included 7 consecutive days of injections unpaired and paired to the test environment demonstrated that ketamine paired to the open field produced a conditioned locomotor response following a challenge with saline, even after 2 days of ketamine withdrawal. In addition, it was shown that ketamine, when paired to the open field produced context-dependent behavioral sensitization. In summary, 30 mg/kg of ketamine developed and expressed a sensitized locomotor response, which was inhibited both by D2 and 5-HT2 antagonism. Interestingly the same dose interacted with environmental factors, resulting in a conditioned locomotor response and a context-dependent sensitization. Therefore, this study suggests a key role of both D2 and 5-HT2 receptors and the environmental context in the ketamine-induced behavioral sensitization.O antagonista não competitivo de receptores NMDA, cetamina, teve seu uso restrito na medicina humana devido aos seus efeitos secundários, atribuídos a doses subanestésicas. Atualmente além dessa droga ser utilizada como modelo experimental da esquizofrenia, também é usada de forma recreativa. Visto a contribuição da sensibilização comportamental ao estudo de efeitos antipsicóticos e da drogadição, o presente trabalho objetivou: no experimento 1 (exp1) avaliar o desenvolvimento e a expressão da sensibilização comportamental induzida por doses subanestésicas (30 e 50 mg/kg) de cetamina; nos experimentos 2 e 3 (exp2 e exp3), respectivamente, investigar o papel dos antagonistas D2, racloprida, e 5-HT2, cetanserina; e, por último, no experimento 4 (exp4) avaliar a habilidade da cetamina em produzir resposta locomotora tanto condicionada quanto contextualmente sensibilizada. Para isso, camundongos suíços adultos foram submetidos a 3 dias consecutivos de habituações no campo aberto por 60 (exp1) ou 20 (exp2-3-4) minutos. Após a fase de habituação, cada experimento seguiu seus procedimentos específicos. No exp1, 7 dias consecutivos de exposição a 30 ou 50 mg/kg de cetamina mostraram que a dose de 30 mg/kg desenvolveu uma resposta locomotora sensibilizada e após 5 dias de retirada essa mesma dose expressou também uma resposta locomotora sensibilizada. Devido ao sucesso dessa dose e a não diferença entre os sexos, adotou-se utilizar animais machos e a dose de 30 mg/kg nos demais experimentos. No exp2, o tratamento por 7 dias consecutivos de cetamina antecedida por racloprida mostrou que o bloqueio de D2 preveniu tanto o desenvolvimento quanto a expressão da sensibilização comportamental produzida por cetamina, mesmo a racloprida per se não diminuindo a locomoção. Consistentemente, o exp3 mostrou prevenção de ambas as respostas quando a cetamina foi precedida pelo antagonista 5-HT2, cetanserina. Por fim, o exp4, com o esquema de 7 repetições diárias de injeções não associadas e associadas ao ambiente teste, mostrou que a cetamina administrada de forma associada produziu locomoção condicionada mediante ao desafio de salina após dois dias de retirada. Além disso, foi mostrado que a cetamina administrada de forma associada produziu sensibilização dependente do contexto ambiental. Em suma, a cetamina na dose de 30 mg/kg desenvolveu e expressou uma resposta locomotora sensibilizada, a qual foi prevenida tanto pelo antagonismo de D2 quanto pelo de 5-HT2. Curiosamente a mesma dose interagiu com fatores ambientais, resultando numa locomoção condicionada e numa sensibilização dependente do contexto. Portanto, o presente trabalho sugere um papel fundamental tanto dos receptores D2 e 5-HT2 quanto do contexto ambiental na evocação da sensibilização comportamental produzida por cetamina.Submitted by Heloísa CB/A (helobdtd@gmail.com) on 2022-08-22T16:21:10Z No. of bitstreams: 1 Jefferson Pires Galvanho da Costa.pdf: 2117542 bytes, checksum: f9d6322a6f31d0a1beed4f93404238ce (MD5)Made available in DSpace on 2022-08-22T16:21:10Z (GMT). No. of bitstreams: 1 Jefferson Pires Galvanho da Costa.pdf: 2117542 bytes, checksum: f9d6322a6f31d0a1beed4f93404238ce (MD5) Previous issue date: 2016-02-29Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro - FAPERJapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Fisiopatologia Clínica e ExperimentalUERJBrasilCentro Biomédico::Faculdade de Ciências MédicasKetamineBehavioral sensitizationD2 dopamine receptorRaclopride5-HT2 serotonin receptorKetanserinConditioned locomotionContext-dependent behavioral sensitizationCetaminaSensibilização comportamentalReceptor dopaminérgico D2RaclopridaReceptor serotoninérgico 5-HT2CetanserinaLocomoção condicionadaSensibilização comportamental dependente do contextoCIENCIAS BIOLOGICASA participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetaminaRole of D2 and 5-HT2 receptors and the environmental influence on the locomotor response to ketamineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALJefferson Pires Galvanho da Costa.pdfJefferson Pires Galvanho da Costa.pdfapplication/pdf2117542http://www.bdtd.uerj.br/bitstream/1/18251/2/Jefferson+Pires+Galvanho+da+Costa.pdff9d6322a6f31d0a1beed4f93404238ceMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/18251/1/license.txte5502652da718045d7fcd832b79fca29MD511/182512024-02-26 16:36:26.236oai:www.bdtd.uerj.br:1/18251Tk9UQTogTElDRU7Dh0EgUkVERSBTSVJJVVMKRXN0YSBsaWNlbsOnYSBkZSBleGVtcGxvIMOpIGZvcm5lY2lkYSBhcGVuYXMgcGFyYSBmaW5zIGluZm9ybWF0aXZvcy4KCkxJQ0VOw4dBIERFIERJU1RSSUJVScOHw4NPIE7Dg08tRVhDTFVTSVZBCgpDb20gYSBhcHJlc2VudGHDp8OjbyBkZXN0YSBsaWNlbsOnYSwgdm9jw6ogKG8gYXV0b3IgKGVzKSBvdSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGRlIGF1dG9yKSBjb25jZWRlIMOgIFVuaXZlcnNpZGFkZSAKZG8gRXN0YWRvIGRvIFJpbyBkZSBKYW5laXJvIChVRVJKKSBvIGRpcmVpdG8gbsOjby1leGNsdXNpdm8gZGUgcmVwcm9kdXppciwgIHRyYWR1emlyIChjb25mb3JtZSBkZWZpbmlkbyBhYmFpeG8pLCBlL291IApkaXN0cmlidWlyIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0csO0bmljbyBlIAplbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFVFUkogcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250ZcO6ZG8sIHRyYW5zcG9yIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAKcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBhIFVFUkogcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGEgc3VhIHRlc2Ugb3UgCmRpc3NlcnRhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIApuZXN0YSBsaWNlbsOnYS4gVm9jw6ogdGFtYsOpbSBkZWNsYXJhIHF1ZSBvIGRlcMOzc2l0byBkYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG7Do28sIHF1ZSBzZWphIGRlIHNldSAKY29uaGVjaW1lbnRvLCBpbmZyaW5nZSBkaXJlaXRvcyBhdXRvcmFpcyBkZSBuaW5ndcOpbS4KCkNhc28gYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIGNvbnRlbmhhIG1hdGVyaWFsIHF1ZSB2b2PDqiBuw6NvIHBvc3N1aSBhIHRpdHVsYXJpZGFkZSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMsIHZvY8OqIApkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgw6AgVUVSSiBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgCmlkZW50aWZpY2FkbyBlIHJlY29uaGVjaWRvIG5vIHRleHRvIG91IG5vIGNvbnRlw7pkbyBkYSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gb3JhIGRlcG9zaXRhZGEuCgpDQVNPIEEgVEVTRSBPVSBESVNTRVJUQcOHw4NPIE9SQSBERVBPU0lUQURBIFRFTkhBIFNJRE8gUkVTVUxUQURPIERFIFVNIFBBVFJPQ8ONTklPIE9VIApBUE9JTyBERSBVTUEgQUfDik5DSUEgREUgRk9NRU5UTyBPVSBPVVRSTyBPUkdBTklTTU8gUVVFIE7Dg08gU0VKQSBFU1RBClVOSVZFUlNJREFERSwgVk9Dw4ogREVDTEFSQSBRVUUgUkVTUEVJVE9VIFRPRE9TIEUgUVVBSVNRVUVSIERJUkVJVE9TIERFIFJFVklTw4NPIENPTU8gClRBTULDiU0gQVMgREVNQUlTIE9CUklHQcOHw5VFUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKQSBVbml2ZXJzaWRhZGUgZG8gRXN0YWRvIGRvIFJpbyBkZSBKYW5laXJvIChVRVJKKSBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lIChzKSBvdSBvKHMpIG5vbWUocykgZG8ocykgCmRldGVudG9yKGVzKSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzIApjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgo=Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T19:36:26Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
dc.title.alternative.eng.fl_str_mv |
Role of D2 and 5-HT2 receptors and the environmental influence on the locomotor response to ketamine |
title |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
spellingShingle |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina Costa, Jefferson Pires Galvanho da Ketamine Behavioral sensitization D2 dopamine receptor Raclopride 5-HT2 serotonin receptor Ketanserin Conditioned locomotion Context-dependent behavioral sensitization Cetamina Sensibilização comportamental Receptor dopaminérgico D2 Racloprida Receptor serotoninérgico 5-HT2 Cetanserina Locomoção condicionada Sensibilização comportamental dependente do contexto CIENCIAS BIOLOGICAS |
title_short |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
title_full |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
title_fullStr |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
title_full_unstemmed |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
title_sort |
A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina |
author |
Costa, Jefferson Pires Galvanho da |
author_facet |
Costa, Jefferson Pires Galvanho da jfgalvanho@yahoo.com.br |
author_role |
author |
author2 |
jfgalvanho@yahoo.com.br |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Villaça, Yael de Abreu |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2110538573461886 |
dc.contributor.referee1.fl_str_mv |
Carrera, Marinete Pinheiro |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/1314413290192367 |
dc.contributor.referee2.fl_str_mv |
Pandolfo, Pablo |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/8700964351768486 |
dc.contributor.referee3.fl_str_mv |
Daltro-Santos, Penha Cristina Barradas |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/9817163660114748 |
dc.contributor.referee4.fl_str_mv |
Carvalho, Anderson Ribeiro |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9437798241357566 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2070422598048012 |
dc.contributor.author.fl_str_mv |
Costa, Jefferson Pires Galvanho da jfgalvanho@yahoo.com.br |
contributor_str_mv |
Villaça, Yael de Abreu Carrera, Marinete Pinheiro Pandolfo, Pablo Daltro-Santos, Penha Cristina Barradas Carvalho, Anderson Ribeiro |
dc.subject.eng.fl_str_mv |
Ketamine Behavioral sensitization D2 dopamine receptor Raclopride 5-HT2 serotonin receptor Ketanserin Conditioned locomotion Context-dependent behavioral sensitization |
topic |
Ketamine Behavioral sensitization D2 dopamine receptor Raclopride 5-HT2 serotonin receptor Ketanserin Conditioned locomotion Context-dependent behavioral sensitization Cetamina Sensibilização comportamental Receptor dopaminérgico D2 Racloprida Receptor serotoninérgico 5-HT2 Cetanserina Locomoção condicionada Sensibilização comportamental dependente do contexto CIENCIAS BIOLOGICAS |
dc.subject.por.fl_str_mv |
Cetamina Sensibilização comportamental Receptor dopaminérgico D2 Racloprida Receptor serotoninérgico 5-HT2 Cetanserina Locomoção condicionada Sensibilização comportamental dependente do contexto |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS |
description |
Ketamine, a non-competitive NMDA receptor antagonist had its use restricted in human medicine because of its side effects attributed to subanesthetic doses. Currently, this drug is used as an experimental model of schizophrenia and also recreationally. Considering the contribution of behavioral sensitization to the study of antipsychotic effects and drug addiction, the present study was subdivided into 4 experiments. Experiment 1 (exp1) aimed to evaluate the development and expression of behavioral sensitization induced by subanesthetic doses (30 and 50 mg/kg) of ketamine. In experiments 2 and 3 (exp2 and exp3), the objectives were to investigate the role of the D2 and the 5-HT2 antagonists, raclopride and ketanserin, respectively. Finally, experiment 4 (exp4) aimed to evaluate the ability of ketamine to produce both conditioned and contextually sensitized locomotor responses. Initially, adult Swiss mice were submitted to 3 consecutive days of habituation in the open field for 60 (exp1) or 20 (exp2-3-4) minutes each day. After the habituation phase, each experiment followed its specific procedures. As for exp 1, seven consecutive days of exposure to 30 or 50 mg/kg ketamine demonstrated that 30 mg/kg produced the development of a sensitized locomotor response and, after 5 days of withdrawal, this same dose expressed a sensitized locomotor response. Based on these effects and on the lack of differences between males and females, for the next set of experiments we selected 30 mg/kg of ketamine to be administered in males. In exp2, 7 consecutive days of ketamine preceded by raclopride exposure indicated that the D2 blockade prevented both the development and expression of ketamine-induced behavioral sensitization, even in the absence of raclopride locomotor effects. Consistently, exp3 showed that the prevention of both responses occurred when ketamine was preceded by the 5-HT2 antagonist, ketanserin. Finally, in exp 4, the experimental protocol that included 7 consecutive days of injections unpaired and paired to the test environment demonstrated that ketamine paired to the open field produced a conditioned locomotor response following a challenge with saline, even after 2 days of ketamine withdrawal. In addition, it was shown that ketamine, when paired to the open field produced context-dependent behavioral sensitization. In summary, 30 mg/kg of ketamine developed and expressed a sensitized locomotor response, which was inhibited both by D2 and 5-HT2 antagonism. Interestingly the same dose interacted with environmental factors, resulting in a conditioned locomotor response and a context-dependent sensitization. Therefore, this study suggests a key role of both D2 and 5-HT2 receptors and the environmental context in the ketamine-induced behavioral sensitization. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-02-29 |
dc.date.accessioned.fl_str_mv |
2022-08-22T16:21:10Z |
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.citation.fl_str_mv |
GALVANHO, Jefferson Pires. A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina. 2016. 107 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) – Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2016. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/18251 |
identifier_str_mv |
GALVANHO, Jefferson Pires. A participação dos receptores D2 e 5-HT2 e a influência do ambiente sobre a resposta locomotora induzida por cetamina. 2016. 107 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) – Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2016. |
url |
http://www.bdtd.uerj.br/handle/1/18251 |
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 |
dc.publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Fisiopatologia Clínica e Experimental |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Faculdade de Ciências Médicas |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
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Universidade do Estado do Rio de Janeiro (UERJ) |
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UERJ |
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UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ |
bitstream.url.fl_str_mv |
http://www.bdtd.uerj.br/bitstream/1/18251/2/Jefferson+Pires+Galvanho+da+Costa.pdf http://www.bdtd.uerj.br/bitstream/1/18251/1/license.txt |
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MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
repository.mail.fl_str_mv |
bdtd.suporte@uerj.br |
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1792352217173327872 |