Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos

Detalhes bibliográficos
Autor(a) principal: Tomazi, Lediane
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações do UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/9019
Resumo: The morphine addiction is a chronic disease that involves biological, cognitive and behavioral changes developed after repeated and compulsive drug use. Even after long periods of abstinence relapses occur to users, especially when faced with situations that resemble the use thereof. The protocol of conditioned place preference (CPP) has been one of the most widely used experimental models to measure the positive reinforcing effects (conditioned place preference) and negative (conditioned place aversion) of several drugs, including morphine. Studies show that antagonists of the N-methyl-D-aspartate (NMDA) block morphine-induced CPP, suggesting that this receptor is involved in the effects of morphine. Since polyamines act at the NMDA receptor, spermidine (SPD) positive allosteric modulating shape and arcaine acting as an antagonist of the polyamine site on this receiver, the purpose of this study the effect of polyamines on the preference induced conditioned place was to evaluate morphine. Adult male Swiss mice were pre-conditioned once a day for 15 minutes for two consecutive device in the CPP, the next day days were subjected twice daily for conditioning sessions with different drugs and protocols for four consecutive days. Twenty-four hours after the last conditioning session the animals were subjected to the test. The CPP score was calculated for the time spent in the compartment paired with the drug on test day, minus the time spent in the same compartment on the second day of the preconditioning. The results of this study showed that morphine (2.5-10 mg/kg, ip) induced CPP, but not aversion induced conditioned place aversion, the SPD (3-30 mg/kg, ip) and arcaine (0.3-3 mg/kg, ip) did not preferably nor induced conditioned place aversion. However, arcaine (3 mg/kg) administered 15 min before morphine (5 mg/kg) attenuated the pre-training acquisition of morphine-induced PCL. The arcaine (3 mg/kg) administered immediately after conditioning with morphine (5 mg/kg) blocked morphine induced PCL. Also, arcaine (3 mg/kg) administered 30 min pretest blocked morphine induced expression CPP. Furthermore, the effect of arcaine on attenuate the effect of morphine was prevented by the administration of SPD before conditioning, but was not reversed by postconditioning pre-test administration and SPD. These data indicate that arcaine blocks the rewarding effect of morphine and arcaine suggests that it could be a therapeutic target in the development of drugs to treat addiction to morphine.
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spelling 2015-11-062015-11-062014-08-13TOMAZI, Lediane. ARCAINE REVERSE THE MORPHINE-INDUCED CONDITIONED PLACE PREFERENCE IN MICE. 2014. 66 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/9019The morphine addiction is a chronic disease that involves biological, cognitive and behavioral changes developed after repeated and compulsive drug use. Even after long periods of abstinence relapses occur to users, especially when faced with situations that resemble the use thereof. The protocol of conditioned place preference (CPP) has been one of the most widely used experimental models to measure the positive reinforcing effects (conditioned place preference) and negative (conditioned place aversion) of several drugs, including morphine. Studies show that antagonists of the N-methyl-D-aspartate (NMDA) block morphine-induced CPP, suggesting that this receptor is involved in the effects of morphine. Since polyamines act at the NMDA receptor, spermidine (SPD) positive allosteric modulating shape and arcaine acting as an antagonist of the polyamine site on this receiver, the purpose of this study the effect of polyamines on the preference induced conditioned place was to evaluate morphine. Adult male Swiss mice were pre-conditioned once a day for 15 minutes for two consecutive device in the CPP, the next day days were subjected twice daily for conditioning sessions with different drugs and protocols for four consecutive days. Twenty-four hours after the last conditioning session the animals were subjected to the test. The CPP score was calculated for the time spent in the compartment paired with the drug on test day, minus the time spent in the same compartment on the second day of the preconditioning. The results of this study showed that morphine (2.5-10 mg/kg, ip) induced CPP, but not aversion induced conditioned place aversion, the SPD (3-30 mg/kg, ip) and arcaine (0.3-3 mg/kg, ip) did not preferably nor induced conditioned place aversion. However, arcaine (3 mg/kg) administered 15 min before morphine (5 mg/kg) attenuated the pre-training acquisition of morphine-induced PCL. The arcaine (3 mg/kg) administered immediately after conditioning with morphine (5 mg/kg) blocked morphine induced PCL. Also, arcaine (3 mg/kg) administered 30 min pretest blocked morphine induced expression CPP. Furthermore, the effect of arcaine on attenuate the effect of morphine was prevented by the administration of SPD before conditioning, but was not reversed by postconditioning pre-test administration and SPD. These data indicate that arcaine blocks the rewarding effect of morphine and arcaine suggests that it could be a therapeutic target in the development of drugs to treat addiction to morphine.A adicção a morfina consiste em uma doença crônica que envolve alterações biológicas, cognitivas e comportamentais desenvolvida após o uso repetido e compulsivo da droga. Mesmo após longos períodos de abstinência ocorrem recaídas aos usuários, principalmente quando se deparam com situações que lembram o uso da mesma. O protocolo de preferência condicionada por lugar (PCL) tem sido um dos modelos experimentais mais utilizados para mensurar os efeitos reforçadores positivos (preferência condicionada por lugar) e os negativos (aversão condicionada por lugar) de diversas drogas, incluindo a morfina. Estudos mostram que antagonistas do receptor N-Metil-D-Aspartato (NMDA) bloqueiam a PCL induzida por morfina, sugerindo que este receptor está envolvido nos efeitos da morfina. Uma vez que as poliaminas atuam no receptor NMDA, a espermidina (SPD) modulando de forma alostérica positiva e a arcaína agindo como antagonista do sítio das poliaminas neste receptor, o objetivo deste estudo foi avaliar o efeito das poliaminas sobre a preferência condicionada por lugar induzida por morfina. Camundongos Swiss machos foram pré-condicionados uma vez por dia, durante 15 minutos por dois dias consecutivos no aparelho de PCL, no dia seguinte, foram submetidos, duas vezes por dia às sessões de condicionamento, com diferentes drogas e protocolos durante quatro dias consecutivos. Vinte e quatro horas após a última sessão de condicionamento os animais foram submetidos ao teste. O escore de PCL foi calculado pelo tempo gasto no compartimento pareado com a droga no dia do teste, menos o tempo gasto no mesmo compartimento no segundo dia do pré-condicionamento. Os resultados deste estudo mostraram que a morfina (2,5-10 mg/kg, i.p.) induziu PCL, mas não aversão condicionada por lugar, a SPD (3-30 mg/kg, i.p.) e arcaína (0,3-3 mg/kg, i.p.) não induziram preferência e nem aversão condicionada por lugar. No entanto, a arcaína (3 mg/kg) administrada 15 minutos antes da morfina (5 mg/kg) no pré-treino atenuou a aquisição da PCL induzida por morfina. A arcaína (3 mg/kg) administrada imediatamente após o condicionamento com morfina (5 mg/kg) bloqueou PCL induzida por morfina. Ainda, arcaína (3 mg/kg) administrada 30 min pré-teste bloqueou a expressão PCL induzida por morfina. Além disso, o efeito da arcaína em atenuar o efeito da morfina foi prevenido pela administração de SPD antes do condicionamento, mas não foi revertido pela administração pós-condicionamento e pré-teste de SPD. Estes dados indicam que arcaína bloqueia o efeito de recompensa da morfina e sugere que a arcaína poderia ser um alvo terapêutico no desenvolvimento de drogas para tratar a adicção por morfina.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaArcaínaEspermidinaMorfinaPreferência condicionada por lugarReceptor NMDAArcaineSpermidineMorphineConditioned place preferenceNMDA receptorCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAArcaína reverte a preferência condicionada por lugar induzida por morfina em camundongosArcaine reverse the morphine-induced conditioned place preference in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisRubin, Maribel Antonellohttp://lattes.cnpq.br/7237734243628134Burger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Oliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902http://lattes.cnpq.br/2153897592911471Tomazi, Lediane20100000000040050030050050017f72a93-232f-40b3-9c14-1b54b978789b80abda3d-2f0c-4d68-961b-a57ff77e36709ba38641-32d0-45d3-92ea-7987f1ae97da4bf6b0f2-e678-4638-8254-7ffc6b173f0finfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTOMAZI, LEDIANE.pdfapplication/pdf1421514http://repositorio.ufsm.br/bitstream/1/9019/1/TOMAZI%2c%20LEDIANE.pdfe6b36a5203130743f0b6a6c6b3f66c77MD51TEXTTOMAZI, LEDIANE.pdf.txtTOMAZI, LEDIANE.pdf.txtExtracted texttext/plain144585http://repositorio.ufsm.br/bitstream/1/9019/2/TOMAZI%2c%20LEDIANE.pdf.txt109dd893a7f1c28d60cc8aeece488847MD52THUMBNAILTOMAZI, LEDIANE.pdf.jpgTOMAZI, LEDIANE.pdf.jpgIM Thumbnailimage/jpeg4818http://repositorio.ufsm.br/bitstream/1/9019/3/TOMAZI%2c%20LEDIANE.pdf.jpg9a5d43210034f2bf78186c3319641ec0MD531/90192022-03-03 08:28:56.548oai:repositorio.ufsm.br:1/9019Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-03-03T11:28:56Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.por.fl_str_mv Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
dc.title.alternative.eng.fl_str_mv Arcaine reverse the morphine-induced conditioned place preference in mice
title Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
spellingShingle Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
Tomazi, Lediane
Arcaína
Espermidina
Morfina
Preferência condicionada por lugar
Receptor NMDA
Arcaine
Spermidine
Morphine
Conditioned place preference
NMDA receptor
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
title_full Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
title_fullStr Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
title_full_unstemmed Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
title_sort Arcaína reverte a preferência condicionada por lugar induzida por morfina em camundongos
author Tomazi, Lediane
author_facet Tomazi, Lediane
author_role author
dc.contributor.advisor1.fl_str_mv Rubin, Maribel Antonello
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/7237734243628134
dc.contributor.referee1.fl_str_mv Burger, Marilise Escobar
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/9128090974948413
dc.contributor.referee2.fl_str_mv Oliveira, Sara Marchesan de
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/6574555059806902
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/2153897592911471
dc.contributor.author.fl_str_mv Tomazi, Lediane
contributor_str_mv Rubin, Maribel Antonello
Burger, Marilise Escobar
Oliveira, Sara Marchesan de
dc.subject.por.fl_str_mv Arcaína
Espermidina
Morfina
Preferência condicionada por lugar
Receptor NMDA
topic Arcaína
Espermidina
Morfina
Preferência condicionada por lugar
Receptor NMDA
Arcaine
Spermidine
Morphine
Conditioned place preference
NMDA receptor
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
dc.subject.eng.fl_str_mv Arcaine
Spermidine
Morphine
Conditioned place preference
NMDA receptor
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description The morphine addiction is a chronic disease that involves biological, cognitive and behavioral changes developed after repeated and compulsive drug use. Even after long periods of abstinence relapses occur to users, especially when faced with situations that resemble the use thereof. The protocol of conditioned place preference (CPP) has been one of the most widely used experimental models to measure the positive reinforcing effects (conditioned place preference) and negative (conditioned place aversion) of several drugs, including morphine. Studies show that antagonists of the N-methyl-D-aspartate (NMDA) block morphine-induced CPP, suggesting that this receptor is involved in the effects of morphine. Since polyamines act at the NMDA receptor, spermidine (SPD) positive allosteric modulating shape and arcaine acting as an antagonist of the polyamine site on this receiver, the purpose of this study the effect of polyamines on the preference induced conditioned place was to evaluate morphine. Adult male Swiss mice were pre-conditioned once a day for 15 minutes for two consecutive device in the CPP, the next day days were subjected twice daily for conditioning sessions with different drugs and protocols for four consecutive days. Twenty-four hours after the last conditioning session the animals were subjected to the test. The CPP score was calculated for the time spent in the compartment paired with the drug on test day, minus the time spent in the same compartment on the second day of the preconditioning. The results of this study showed that morphine (2.5-10 mg/kg, ip) induced CPP, but not aversion induced conditioned place aversion, the SPD (3-30 mg/kg, ip) and arcaine (0.3-3 mg/kg, ip) did not preferably nor induced conditioned place aversion. However, arcaine (3 mg/kg) administered 15 min before morphine (5 mg/kg) attenuated the pre-training acquisition of morphine-induced PCL. The arcaine (3 mg/kg) administered immediately after conditioning with morphine (5 mg/kg) blocked morphine induced PCL. Also, arcaine (3 mg/kg) administered 30 min pretest blocked morphine induced expression CPP. Furthermore, the effect of arcaine on attenuate the effect of morphine was prevented by the administration of SPD before conditioning, but was not reversed by postconditioning pre-test administration and SPD. These data indicate that arcaine blocks the rewarding effect of morphine and arcaine suggests that it could be a therapeutic target in the development of drugs to treat addiction to morphine.
publishDate 2014
dc.date.issued.fl_str_mv 2014-08-13
dc.date.accessioned.fl_str_mv 2015-11-06
dc.date.available.fl_str_mv 2015-11-06
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dc.identifier.citation.fl_str_mv TOMAZI, Lediane. ARCAINE REVERSE THE MORPHINE-INDUCED CONDITIONED PLACE PREFERENCE IN MICE. 2014. 66 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014.
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/9019
identifier_str_mv TOMAZI, Lediane. ARCAINE REVERSE THE MORPHINE-INDUCED CONDITIONED PLACE PREFERENCE IN MICE. 2014. 66 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014.
url http://repositorio.ufsm.br/handle/1/9019
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