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- ItemAcesso aberto (Open Access)Avaliação fitoquímica e dos efeitos sobre o Sistema Nervoso Central de cinco espécies de Maracujá (Passiflora)(Universidade Federal de São Paulo (UNIFESP), 2010-08-25) Sakalem, Marna Eliana [UNIFESP]; Carlini, Elisaldo Araujo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Os distúrbios de ansiedade são o tipo de transtorno psiquiátrico mais comum entre a população mundial. Um dos fármacos mais utilizados atualmente para tratá-los são os benzodiazepínicos, mas estes apresentam algumas reações adversas, entre elas sedação, sonolência, déficit cognitivo, relaxamento muscular, além de causarem dependência. A busca por tratamentos alternativos para a ansiedade foi o objetivo do presente trabalho. Foram avaliadas cinco espécies de Passiflora, gênero muito bem adaptado ao Brasil.: P. bahiensis, P. coccinea, P. quadrangularis, P. sidaefolia e P. vitifolia. Foi realizada um screening farmacológica, teste de toxicidade, além da avaliação do efeito ansiolítico dos extratos, em camundongos e ratos. Os resultados mostraram que três das cinco espécies (P. coccinea, P. quadrangularis e P. sidaefolia) reduziram a atividade motora dos animais, uma interferiu na latência de sono (P. coccinea), e nenhuma alterou a coordenação motora. Três espécies (P. coccinea, P. quadrangularis e P. vitifolia) apresentaram alta toxicidade por via intraperitoneal. Nenhuma apresentou efeito tipo ansiolítico no Labirinto em Cruz Elevado, mas uma delas, P. sidaefolia, aumentou o número de mergulhos no teste da Placa Perfurada. Este dado, conjuntamente com a análise fitoquímica, a qual revelou oito diferentes flavonas C-glicosiladas, conferem a esta espécie um possível potencial ansiolítico.
- ItemAcesso aberto (Open Access)Efeito do estresse crônico de derrota social em camundongos sobre a ansiedade e preferência social: Possível reversão com dose aguda de etanol(Universidade Federal de São Paulo (UNIFESP), 2018-10-25) Mori, Marcos Vinicius [UNIFESP]; Quadros, Isabel Marian Hartmann de [UNIFESP]; http://lattes.cnpq.br/3982014468609862; http://lattes.cnpq.br/2311269855631778; Universidade Federal de São Paulo (UNIFESP)Chronic stress results in deleterious effects on individuals, and social stress is one of the most recurring forms of stress nowadays. Alcohol can influence the behavior of individuals in different ways. In this study, the acute effects of alcohol were analyzed in mice submitted either to continuous social defeat or the episodic social defeat stress. Our hypothesis is that social stress would produce an anxiogenic effect on the elevated plus maze and a reduction in social investigation, and that a single dose of alcohol would reverse these effects of stress. Male adult Swiss mice were exposed to a 10-day protocol of either continuous social defeat stress, or episodic defeat stress. After 4 to 7 days, animals were allocated in 4 groups (control saline, stress saline, control alcohol and stress alcohol) and were tested in two models, the elevated plus maze and the social investigation, in separate experiments. Chronic exposure to both continuous and episodic social stress failed to affect the behavior on the elevated plus maze, but an anxiolytic effect of a single dose of 1,0 g/kg of alcohol was observed. In the social investigation test, control saline and control alcohol groups showed preference to exploring the social target, while the animals of control stress showed either aversion (in case of continuous stress) or lack of interest (in case of episodic stress) to the social target. In both cases, the administration of a single low dose of alcohol (0,25 g/kg i.p.) resulted in either an attenuation (in case of the continuous stress) or a reversion (in case of the episodic stress) of the effects of the social defeat, showing that a single dose of alcohol prevented social deficits in stressed animals, which could facilitate the development of alcohol addiction on these animals.
- ItemAcesso aberto (Open Access)Efeitos da suplementação com ÔMEGA-3 em ratos Wistar durante o período de lactação sobre o comportamento emocional de mães e filhotes submetidos à separação materna longa(Universidade Federal de São Paulo (UNIFESP), 2010-04-28) Rocha, Janaina da Silva [UNIFESP]; Suchecki, Deborah [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Several studies have shown that polyunsaturated fatty acids, specially omega-3, or n-3, are essential for good health and for normal development. Such compounds, along with their active metabolites, are also important to the structural and physiological maintenance of the central nervous system throughout development, mainly during the initial phases of life. Therefore, we studied the effects of n-3 supplementation on dams and pups submitted the long maternal separation (LMS, 360 min long), from 2 to 14 post natal day (pnd). This is a stressfull stimulus to both parts. Pregnant female Wistar rats, 10-weeks old, were separated into 6 groups: 1) Control (CTL) + regular diet; 2) CTL + soy oil; 3) CTL + fish oil (n-3); 4) LMS + regular diet; 5) LMS + soy oil; 6) LMS + n-3. The supplementation was kept from birthday to weaning, which occurred on pnd 21. Three days after weaning, dams were exposed to the Elevated Plus Maze (EPM), as did the pups, on pnd 31, and three days after the Elevated Plus Maze, dams were evaluated on the Forced Swimming Test (FTS). From PND 83, male and female pups were challenged on EPM and FST. The behavioral consequences of the separation were expressive on dams, but had little influence on the emotionality of young males and females. Surprisingly, n-3 caused an ansiogenic effect on mothers, and failed to cause any effect on pups’ behavior. However, there was a reduction of the basal concentration of corticosterone in young females and an increased reactivity to stress in both male and female adolescents.
- ItemAcesso aberto (Open Access)Possíveis mecanismos envolvidos na ausência do fenômeno de “one trial tolerance” na linhagem de ratos espontaneamente hipertensos – SHR(Universidade Federal de São Paulo (UNIFESP), 2006-01-01) Lopez, Giorgia Batlle [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The phenomenon of “one-trial tolerance” (OTT) refers to the absence of the anxiolytic effect of benzodiazepines following a previous exposure to the elevated plus maze (EPM). In addition to several behavioral differences in relation to normotensive strains, spontaneously hypertensive rats (SHR) do not present the OTT phenomenon. The aim of the present study was to investigate the mechanisms involved in the absence of the OTT phenomenon in SHR. Experiment 1 was designed to characterize the absence of OTT in SHR, under our experimental conditions. Thus, we verified the effects of chlordiazepoxide, a classic anxiolytic agent, on the behavior of Wistar normotensive rats (Wistar) and SHR, exposed for the first or second time to the EPM. Supporting previous data, our results demonstrated a decrease in the basal level of anxiety presented by SHR. As previously observed, we also verified that, in opposition to Wistar rats, the SHR did not present the phenomenon of OTT. In a first series of experiments, we tried to verify if the absence of OTT presented by SHR would be related to possible memory deficits in this strain. Procedures designed to improve learning/memory (a decrease in the interval between the first and second exposure to the EPM or an increase in the duration of the first exposure) were not able to modify the absence of OTT in SHR. In these experiments, we also verified that both strains presented a decrease in the exploration of the open arms of the EPM throughout the fifteen-minute exposure, demonstrating that there was no learning impairment to the open arm avoidance in SHR. Nevertheless, we observed that after an initial decrease in the time spent in the open arms, there is an increase in the motivation to explore the EPM presented only by SHR in the first and second fifteen-minute exposure. Finally, this increase in the exploration of the open arms throughout the second exposure presented by SHR was potentiated by the administration of chlordiazepoxide (whereas the exploration presented by Wistar rats was not altered). In a second series of experiments, we investigated the possible role of anxiety levels in the first exposure in the absence of the phenomenon of OTT in SHR. Fourty-five-day-old rats (which present an increase in the basal level of anxiety when compared to adult animals) and the administration of an anxiogenic drug (pentylenetetrazole) was used to evaluate the effects of chlordiazepoxide on SHR and Wistar rats in a second exposure to the EPM. Both the 45-day-old SHR and the adult SHR treated with pentylenetetrazole presented increased anxiety levels when compared to control adult SHR in the first exposure. Notwithstanding, these procedures (which were able to increase the levels of anxiety of Wistar and SHR strains) did not prevent the absence of the phenomenon of OTT in the SHR nor the presence of this phenomenon in Wistar rats. Taken as a whole, these data confirm the absence of the OTT phenomenon in SHR and suggest that this absence is not related to a possible impairment of open arm avoidance nor to the decreased basal levels of anxiety presented by this strain. Furthermore, the fact that, on the contrary of Wistar rats, SHR presented a return in their motivation to explore the open arms when exposed for a longer period to the EPM allows the suggestion that this strain becomes “bored” faster when submitted to prolonged exposures to the enclosed arms of the EPM. While this suggestion seems to support the solid literature that suggests this strain as a model of attention-deficit/hyperactivity disorder (ADHD), the return of the motivation to explore the open arms could reintroduce the inherent conflict to explore this naturally aversive area. Such conflict, sensitive to the action of the benzodiazepines, could explain the efficacy of this agent in animals previously exposed to the EPM and, thus the absence of the OTT phenomenon.
- ItemAcesso aberto (Open Access)Revisões sistemáticas e meta-análises sobre o efeito da privação de sono na ansiedade em humanos e roedores(Universidade Federal de São Paulo (UNIFESP), 2015-06-30) Pires, Gabriel Natan de Souza [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Tufik, Sergio [UNIFESP]; http://lattes.cnpq.br/1375290481822767; http://lattes.cnpq.br/4951931552005515; http://lattes.cnpq.br/7799496784629692; Universidade Federal de São Paulo (UNIFESP)Introdução: Aumento nos sintomas de ansiedade têm sido relatado como uma das consequências mais comuns da privação de sono. Estudos clínicos parecem ser unânimes em apresentar uma condição de ansiogênese como resultado da falta de sono. Consequentemente, diversos estudos são conduzidos em modelos animais de ansiedade, porém os resultados são internamente inconsistentes e não replicam os dados observados em humanos. Adicionalmente, nota-se que os efeitos da privação de sono sobre a ansiedade nunca foram sistematicamente revisados, tanto em humanos quanto em animais. Objetivos: Para abordar o presente problema translacional, propôs-se conduzir revisões sistemáticas e meta-análises em ambos os contextos. Métodos: Pesquisas bibliográficas foram conduzidas nas bases de dados Pubmed/Medline e Scopus. Para cada artigo selecionado foi calculado o tamanho de efeito por meio do método G de Hedge e o tamanho de efeito global foi medido pelo método de efeitos randômicos de Dersimonian e Laird. Heterogeneidade foi medida por meio do teste Q de Cochran e do índice I2. Resultados foram tomados como significativos quando o intervalo de confiança do tamanho de efeito a 95% era inteiramente maior ou menor que zero, associado a um p<0,05. Resultados: Ao total, 756 artigos foram selecionados em primeira instância, gerando uma amostra final de 18 artigos e 34 experimentos para a meta-análise em pesquisa clínica e de 50 artigos e 81 experimentos para a meta-análise em pesquisa com animais de experimentação. Na meta-análise de estudos em seres humanos, observou-se ansiogênese como resultado da privação de sonos na maior das análises feitas [0,39 (0,67; 0,11); I2: 0,72; p<0,01], condição replicada em boa parte das análises estratificadas. Em contrapartida, os dados em animais demonstraram o surgimento de uma condição de ansiólise [-0,78 (-1,18; -0,38); I2=0,90; p<0,01], oposta ao observado em seres humanos, fato corroborado na grande maioria das análises estratificadas. Conclusão: Estes resultados evidenciam a falta de replicabilidade entre estes dois âmbitos de pesquisa e a incapacidade dos atuais modelos de avaliação de ansiedade em pesquisa básica de reproduzir os achados encontrados em seres humanos.