Análise etoexperimental de modelos de ansiedade após intoxicação de etanol em camundongos C57Bl/6 fêmeas e machos
Data
2024-12-17
Autores
Cecyn, Marianna Nogueira 
Orientadores
Abrahão, Karina Possa
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Os camundongos são presas na natureza, portanto necessitam fazer um balanço da decisão de exploração do ambiente e se manter protegido. Comportamentos de avaliação de risco são importantes para a tomada de. Algumas drogas são capazes de modificar esse balanço entre exploração e defesa, dentre elas o álcool. Apesar da literatura já ter explorado os efeitos do etanol nos comportamentos defensivos e exploratórios, poucos estudos investigam a interação de intoxicações pesadas com intoxicações mais leves em machos e fêmeas, ou abordam a questão com uma análise etoexperimental. Objetivo: Investigar os efeitos de uma dose ansiolítica de etanol nos comportamentos de exploração e de avaliação de risco em animais que foram expostos repetidamente à intoxicação pesada de etanol na adolescência, considerando a variável sexo. Métodos: Foram utilizados camundongos C57Bl6 fêmeas e machos, entre seis e nove semanas de idade. A intoxicação pesada por 4,0 g/kg de etanol ou salina (0,9% NaCl) foi realizada duas vezes por semana, com intervalo de 48 horas, por duas semanas, quando utilizamos a perda de reflexo postural (LORR) como medida dos efeitos depressores do álcool. Na semana seguinte ao último episódio de intoxicação, os animais foram submetidos a testes de comportamento do tipo ansioso. No primeiro experimento, os animais receberam uma dose ansiolítica de 1,2 g/kg de etanol ou salina, um min antes de serem colocados no Labirinto em Cruz Elevado (EPM). No segundo experimento, os animais foram testados na Caixa Claro Escuro (LDB) e no EPM, com intervalo de 48 horas entre os testes. Foram mensuradas as medidas clássicas de comportamento do tipo ansioso dos testes, para compor uma análise etoexperimental, através da análise frequentista dos comportamentos, suas correlações, e Modelos de Markov para construção de grafos e investigação das probabilidades de transições entre os comportamentos. Resultados: LORR: apenas os machos de 7-8 semanas apresentaram tolerância. Comportamento do tipo ansioso: A dose de 1,2 g/kg de etanol induziu um comportamento ansiolítico apenas no EPM, independente da intoxicação prévia. A dose de 1,2 g/kg diminuiu o comportamento exploratório nos braços fechados e aumentou o comportamento exploratório nos braços abertos do EPM. No LDB, os animais intoxicados apresentaram menor latência para se expor ao lado claro. Em relação à avaliação de risco no EPM, o etanol antes do teste diminuiu esses comportamentos, sendo ainda menor em machos que foram intoxicados previamente. Não observamos fortes efeitos da intoxicação sobre as probabilidades de transição entre os comportamentos. Conclusões: Apesar da intoxicação pesada prévia não ter alterado o efeito ansiolítico do etanol pré-teste no EPM (efeito que não apareceu no LDB), observamos que para os machos ela pode aumentar a tomada de risco, e para as fêmeas pode aumentar o comportamento exploratório do ambiente protegido.
Introduction: Mice are prey in nature, thus they need to balance the decision to explore their environment and stay protected. Risk assessment behaviors are crucial for decision-making. Some drugs can modify this balance between exploration and defense, including alcohol. Although the literature has explored the effects of ethanol on defensive and exploratory behaviors, few studies investigate the interaction of heavy and light intoxications in males and females, or address the issue with an ethoexperimental analysis. Objective: To investigate the effects of an anxiolytic dose of ethanol on exploration and risk assessment behaviors in animals repeatedly exposed to heavy ethanol intoxication during adolescence, considering sex as a variable. Methods: Female and male C57Bl6 mice, aged six to nine weeks, were used. Heavy intoxication with 4.0 g/kg of ethanol or saline (0.9% NaCl) was administered twice a week, with a 48-hour interval, for two weeks, using the loss of righting reflex (LORR) as a measure of alcohol's depressant effects. In the week following the last intoxication episode, the animals underwent anxiety-like behavior tests. In the first experiment, the animals received an anxiolytic dose of 1.2 g/kg of ethanol or saline one minute before being placed in the Elevated Plus Maze (EPM). In the second experiment, the animals were tested in the Light-Dark Box (LDB) and the EPM, with a 48-hour interval between tests. Classical anxiety-like behavior measures from the tests were used to compose an ethoexperimental analysis through frequentist analysis of behaviors, their correlations, and Markov Models for constructing graphs and investigating transition probabilities between behaviors. Results: LORR: Only males aged 7-8 weeks showed tolerance. Anxiety-like behavior: The 1.2 g/kg dose of ethanol induced anxiolytic behavior only in the EPM, regardless of prior intoxication. The 1.2 g/kg dose decreased exploratory behavior in the closed arms and increased exploratory behavior in the open arms of the EPM. In the LDB, intoxicated animals showed a shorter latency to expose themselves to the light side. Regarding risk assessment in the EPM, ethanol before the test decreased these behaviors, being even lower in males previously intoxicated. We did not observe strong effects of intoxication on the transition probabilities between behaviors. Conclusions: Although prior heavy intoxication did not alter the anxiolytic effect of pre-test ethanol in the EPM (an effect not observed in the LDB), we observed that for males, it may increase risk-taking, and for females, it may increase exploratory behavior in the protected environment.
Introduction: Mice are prey in nature, thus they need to balance the decision to explore their environment and stay protected. Risk assessment behaviors are crucial for decision-making. Some drugs can modify this balance between exploration and defense, including alcohol. Although the literature has explored the effects of ethanol on defensive and exploratory behaviors, few studies investigate the interaction of heavy and light intoxications in males and females, or address the issue with an ethoexperimental analysis. Objective: To investigate the effects of an anxiolytic dose of ethanol on exploration and risk assessment behaviors in animals repeatedly exposed to heavy ethanol intoxication during adolescence, considering sex as a variable. Methods: Female and male C57Bl6 mice, aged six to nine weeks, were used. Heavy intoxication with 4.0 g/kg of ethanol or saline (0.9% NaCl) was administered twice a week, with a 48-hour interval, for two weeks, using the loss of righting reflex (LORR) as a measure of alcohol's depressant effects. In the week following the last intoxication episode, the animals underwent anxiety-like behavior tests. In the first experiment, the animals received an anxiolytic dose of 1.2 g/kg of ethanol or saline one minute before being placed in the Elevated Plus Maze (EPM). In the second experiment, the animals were tested in the Light-Dark Box (LDB) and the EPM, with a 48-hour interval between tests. Classical anxiety-like behavior measures from the tests were used to compose an ethoexperimental analysis through frequentist analysis of behaviors, their correlations, and Markov Models for constructing graphs and investigating transition probabilities between behaviors. Results: LORR: Only males aged 7-8 weeks showed tolerance. Anxiety-like behavior: The 1.2 g/kg dose of ethanol induced anxiolytic behavior only in the EPM, regardless of prior intoxication. The 1.2 g/kg dose decreased exploratory behavior in the closed arms and increased exploratory behavior in the open arms of the EPM. In the LDB, intoxicated animals showed a shorter latency to expose themselves to the light side. Regarding risk assessment in the EPM, ethanol before the test decreased these behaviors, being even lower in males previously intoxicated. We did not observe strong effects of intoxication on the transition probabilities between behaviors. Conclusions: Although prior heavy intoxication did not alter the anxiolytic effect of pre-test ethanol in the EPM (an effect not observed in the LDB), we observed that for males, it may increase risk-taking, and for females, it may increase exploratory behavior in the protected environment.
Descrição
Citação
CECYN, Marianna Nogueira. Análise etoexperimental de modelos de ansiedade após intoxicação de etanol em camundongos C57Bl/6 fêmeas e machos. 2024. 170 f. Tese (Doutorado em Psicobiologia) – Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2024.
Palavras-chave
ODS
Não se aplica