Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto

Detalhes bibliográficos
Autor(a) principal: Daldegan-Bueno, Dimitri Henriques [UNIFESP]
Data de Publicação: 2020
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.xhtml?popup=true&id_trabalho=9274964
https://repositorio.unifesp.br/handle/11600/58768
Resumo: Objective: To evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novelenvironment anxiety. Method: Male Wistar rats received 120, 240, 480, 3,600mg/kg of resuspended lyophilised ayahuasca or water by gavage once a day for 30 days; there was also a non-manipulated homecage group. On the 1st and 15th day, animals were placed individually for five minutes into an acrylic cage for behavioural assessment; on the 30th day, animals were placed individually in the open field for 20 minutes, followed by brain perfusion and removal (140min after last ayahuasca administration) for c-Fos immunoreactive analysis. All tests were done 60 minutes after the administration of ayahuasca. A stochastic analysis based on the ethogram of the animals were conducted to analyse the sequential structure of behaviours; weight was recorded during the entire process. Results: Acute low dose (120mg/kg) did not affect the behaviour but when administered repeatedly increased the ambulation and vertical exploration in the open field, while intermediate doses (240 and 480mg/kg) did not affect the behaviour either acutely nor repeatedly. Extreme high dose (3,600mg/kg) decreased vertical exploration both acutely and repeatedly, and animals in this group had a lower weight gain when compared to all groups, possibly due to the adverse effects that ayahuasca may induce; ethological analysis based on the ethogram confirmed these behavioural results. Aya3,600 had more c-Fos expression than water and aya120 in the medial CA1 region of the hippocampus; more expression than homecage, water, and aya120 in the anterior CA3 region of the hippocampus, and more expression than homecage and water in the medial infra-limbic cortex region. On the aya120 group, there was a negative correlation between the medial CA1 of the hippocampus and ambulation, time spent in rearing and a positive correlation between the medial CA1 and freezing behaviour; for aya3,600 there was a negative correlation between the anterior CA3 and time spent in rearing. No behavioural or neurobiological effects related to anxiety assessed by the open field were found. Conclusion: Different doses of repeated administration of ayahuasca have different effects on the exploratory behaviour evaluated by the open field; however, it did not alter the sequential structure of exploratory behaviour, even with an extremely high dose. Higher activation of areas involved in the emotional process and serotonergic pathway add relevant material to the neurobiological literature of ayahuasca - specifically regarding the repeated/chronic ingestion. Extreme high doses of ayahuasca, even when administrated for 30 consecutive days, does not cause severe impairment in rats, providing further data regarding the safety of ayahuasca intake. Finally, our data do not support an anxiolytic effect of repeated ayahuasca related to the exploration of new anxiogenic-environment.
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spelling Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo abertoEffects of repeated ayahuasca administration on behaviour and c-Fos expression in rats exposed to the open fieldAyahuascac-FosOpen-fieldAmygdalaAnxietyEthogramAyahuascac-FosAmígdalaTeste de campo abertoAnsiedadeEtogramaObjective: To evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novelenvironment anxiety. Method: Male Wistar rats received 120, 240, 480, 3,600mg/kg of resuspended lyophilised ayahuasca or water by gavage once a day for 30 days; there was also a non-manipulated homecage group. On the 1st and 15th day, animals were placed individually for five minutes into an acrylic cage for behavioural assessment; on the 30th day, animals were placed individually in the open field for 20 minutes, followed by brain perfusion and removal (140min after last ayahuasca administration) for c-Fos immunoreactive analysis. All tests were done 60 minutes after the administration of ayahuasca. A stochastic analysis based on the ethogram of the animals were conducted to analyse the sequential structure of behaviours; weight was recorded during the entire process. Results: Acute low dose (120mg/kg) did not affect the behaviour but when administered repeatedly increased the ambulation and vertical exploration in the open field, while intermediate doses (240 and 480mg/kg) did not affect the behaviour either acutely nor repeatedly. Extreme high dose (3,600mg/kg) decreased vertical exploration both acutely and repeatedly, and animals in this group had a lower weight gain when compared to all groups, possibly due to the adverse effects that ayahuasca may induce; ethological analysis based on the ethogram confirmed these behavioural results. Aya3,600 had more c-Fos expression than water and aya120 in the medial CA1 region of the hippocampus; more expression than homecage, water, and aya120 in the anterior CA3 region of the hippocampus, and more expression than homecage and water in the medial infra-limbic cortex region. On the aya120 group, there was a negative correlation between the medial CA1 of the hippocampus and ambulation, time spent in rearing and a positive correlation between the medial CA1 and freezing behaviour; for aya3,600 there was a negative correlation between the anterior CA3 and time spent in rearing. No behavioural or neurobiological effects related to anxiety assessed by the open field were found. Conclusion: Different doses of repeated administration of ayahuasca have different effects on the exploratory behaviour evaluated by the open field; however, it did not alter the sequential structure of exploratory behaviour, even with an extremely high dose. Higher activation of areas involved in the emotional process and serotonergic pathway add relevant material to the neurobiological literature of ayahuasca - specifically regarding the repeated/chronic ingestion. Extreme high doses of ayahuasca, even when administrated for 30 consecutive days, does not cause severe impairment in rats, providing further data regarding the safety of ayahuasca intake. Finally, our data do not support an anxiolytic effect of repeated ayahuasca related to the exploration of new anxiogenic-environment.Objetivo: Avaliar os efeitos comportamentais e neurobiológicos da administração repetida de ayahuasca através de um modelo animal de comportamento exploratório em um ambiente novo e ansiogênico. Método: Ratos Wistar machos receberam 120, 240, 480, 3.600mg/kg de ayahuasca liofilizada ressuspendida em água ou água por gavagem uma vez ao dia por 30 dias; houve também um grupo homecage não manipulado. Os animais foram colocados individualmente por 5 minutos em uma caixa de acrílico para avaliação do comportamento no 1° e 15° dia, no 30° dia, os animais foram colocados individualmente no campo aberto por 20 minutos, seguidos de perfusão e remoção do encéfalo (140 minutos após a última administração de ayahausca) para análise de núcleos imunoreativos para c-Fos. Todos os testes foram realizados 60 minutos após a administração da ayahuasca. Foi realizada uma análise estocástica baseada no etograma dos animais para investigar a estrutura sequencial de comportamentos, o peso foi registrado durante todo o processo. Resultados: A dose baixa (120mg/kg) quando administrada de forma aguda não teve efeito no comportamento, mas de forma repetida aumentou a ambulação e a exploração vertical no campo aberto, enquanto as doses intermediarias (240 e 480mg/kg) não afetaram o comportamento de forma aguda nem repetida. A dose mais alta (3.600mg/kg) diminuiu a exploração vertical tanto de forma aguda quanto repetida, os animais desse grupo apresentaram menor ganho de peso quando comparados com todos os grupos, provavelmente devido aos possíveis efeitos adversos induzidos pela ayahausca. A análise etológica baseada no etograma confirmaram esses resultados comportamentais. Aya3.600 teve mais expressão de c-Fos do que água e aya120 na região CA1 medial do hipocampo; mais expressão que o homecage, água e aya120 na região CA3 anterior do hipocampo, e mais expressão que o homecage e água na região medial do córtex infra-límbico. No grupo aya120, houve uma correlação negativa entre o CA1 medial do hipocampo e a ambulação, tempo levantado (rearing) e uma correlação positiva entre o CA1 medial com o comportamento de congelamento (freezing); no grupo aya3.600, houve uma correlação negativa entre o CA3 anterior e o tempo levantado. Não foram encontrados efeitos comportamentais ou neurobiológicos relacionados à ansiedade avaliados pelo campo aberto. Conclusão: Diferentes doses repetidas de ayahuasca demonstraram um perfil de efeito diferente no comportamento exploratório avaliado em pelo campo aberto, mas não alterou a estrutura sequencial do comportamento exploratório, mesmo com uma dose extremamente alta. Uma maior ativação de áreas envolvidas no processo emocional e via serotoninérgica agregam a literatura neurobiológica dos efeitos da ayahuasca - especificamente em relação à ingestão repetida/crônica. Doses extremamente altas de ayahuasca, mesmo administradas por 30 dias consecutivos, não parecem causar comprometimento graves em ratos, fornecendo dados adicionais sobre a segurança da ingestão da ayahuasca. Nossos dados não dão suporte para um efeito ansiolítico da ayahuasca relacionado à exploração de um novo ambiente ansiogênico.Universidade Federal de São Paulo (UNIFESP)Oliveira, Maria Gabriela Menezes de [UNIFESP]http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723159U8http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4432203P6Universidade Federal de São Paulo (UNIFESP)Daldegan-Bueno, Dimitri Henriques [UNIFESP]2020-11-16T16:56:07Z2020-11-16T16:56:07Z2020-07-30info:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/publishedVersion45 p.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.xhtml?popup=true&id_trabalho=9274964DALDEGAN-BUENO, Dimitri Henriques. Effects of repeated ayahuasca administration on behaviour and c-Fos expression in rats exposed to the open field. 2020. 45 f. Dissertação (Mestrado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo.2020 DALDEGAN-BUENO, DIMITRI H.Mestrado.pdfhttps://repositorio.unifesp.br/handle/11600/58768info:eu-repo/semantics/openAccessengreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-03T13:27:48Zoai:repositorio.unifesp.br/:11600/58768Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-03T13:27:48Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
Effects of repeated ayahuasca administration on behaviour and c-Fos expression in rats exposed to the open field
title Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
spellingShingle Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
Daldegan-Bueno, Dimitri Henriques [UNIFESP]
Ayahuasca
c-Fos
Open-field
Amygdala
Anxiety
Ethogram
Ayahuasca
c-Fos
Amígdala
Teste de campo aberto
Ansiedade
Etograma
title_short Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
title_full Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
title_fullStr Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
title_full_unstemmed Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
title_sort Efeitos da administração repetida de ayahuasca no comportamento e na expressão de c-Fos em ratos expostos ao campo aberto
author Daldegan-Bueno, Dimitri Henriques [UNIFESP]
author_facet Daldegan-Bueno, Dimitri Henriques [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Oliveira, Maria Gabriela Menezes de [UNIFESP]
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723159U8
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4432203P6
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Daldegan-Bueno, Dimitri Henriques [UNIFESP]
dc.subject.por.fl_str_mv Ayahuasca
c-Fos
Open-field
Amygdala
Anxiety
Ethogram
Ayahuasca
c-Fos
Amígdala
Teste de campo aberto
Ansiedade
Etograma
topic Ayahuasca
c-Fos
Open-field
Amygdala
Anxiety
Ethogram
Ayahuasca
c-Fos
Amígdala
Teste de campo aberto
Ansiedade
Etograma
description Objective: To evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novelenvironment anxiety. Method: Male Wistar rats received 120, 240, 480, 3,600mg/kg of resuspended lyophilised ayahuasca or water by gavage once a day for 30 days; there was also a non-manipulated homecage group. On the 1st and 15th day, animals were placed individually for five minutes into an acrylic cage for behavioural assessment; on the 30th day, animals were placed individually in the open field for 20 minutes, followed by brain perfusion and removal (140min after last ayahuasca administration) for c-Fos immunoreactive analysis. All tests were done 60 minutes after the administration of ayahuasca. A stochastic analysis based on the ethogram of the animals were conducted to analyse the sequential structure of behaviours; weight was recorded during the entire process. Results: Acute low dose (120mg/kg) did not affect the behaviour but when administered repeatedly increased the ambulation and vertical exploration in the open field, while intermediate doses (240 and 480mg/kg) did not affect the behaviour either acutely nor repeatedly. Extreme high dose (3,600mg/kg) decreased vertical exploration both acutely and repeatedly, and animals in this group had a lower weight gain when compared to all groups, possibly due to the adverse effects that ayahuasca may induce; ethological analysis based on the ethogram confirmed these behavioural results. Aya3,600 had more c-Fos expression than water and aya120 in the medial CA1 region of the hippocampus; more expression than homecage, water, and aya120 in the anterior CA3 region of the hippocampus, and more expression than homecage and water in the medial infra-limbic cortex region. On the aya120 group, there was a negative correlation between the medial CA1 of the hippocampus and ambulation, time spent in rearing and a positive correlation between the medial CA1 and freezing behaviour; for aya3,600 there was a negative correlation between the anterior CA3 and time spent in rearing. No behavioural or neurobiological effects related to anxiety assessed by the open field were found. Conclusion: Different doses of repeated administration of ayahuasca have different effects on the exploratory behaviour evaluated by the open field; however, it did not alter the sequential structure of exploratory behaviour, even with an extremely high dose. Higher activation of areas involved in the emotional process and serotonergic pathway add relevant material to the neurobiological literature of ayahuasca - specifically regarding the repeated/chronic ingestion. Extreme high doses of ayahuasca, even when administrated for 30 consecutive days, does not cause severe impairment in rats, providing further data regarding the safety of ayahuasca intake. Finally, our data do not support an anxiolytic effect of repeated ayahuasca related to the exploration of new anxiogenic-environment.
publishDate 2020
dc.date.none.fl_str_mv 2020-11-16T16:56:07Z
2020-11-16T16:56:07Z
2020-07-30
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.xhtml?popup=true&id_trabalho=9274964
DALDEGAN-BUENO, Dimitri Henriques. Effects of repeated ayahuasca administration on behaviour and c-Fos expression in rats exposed to the open field. 2020. 45 f. Dissertação (Mestrado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo.
2020 DALDEGAN-BUENO, DIMITRI H.Mestrado.pdf
https://repositorio.unifesp.br/handle/11600/58768
url https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.xhtml?popup=true&id_trabalho=9274964
https://repositorio.unifesp.br/handle/11600/58768
identifier_str_mv DALDEGAN-BUENO, Dimitri Henriques. Effects of repeated ayahuasca administration on behaviour and c-Fos expression in rats exposed to the open field. 2020. 45 f. Dissertação (Mestrado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo.
2020 DALDEGAN-BUENO, DIMITRI H.Mestrado.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 45 p.
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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