Impacto da intoxicação alcoólica durante a adolescência nos comportamentos de avaliação de risco e consumo de etanol em camundongos adultos fêmeas e machos
Data
2022-09-30
Autores
Pichinin, Letícia de Souza 
Orientadores
Abrahão, Karina Possa
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A adolescência é a fase final do neurodesenvolvimento e é neste período que usualmente ocorre o início da experimentação de álcool. É popular entre os jovens, o consumo de muitas doses desta droga em um curto período de tempo, o que leva à intoxicação alcoólica. Além da maior vulnerabilidade para acidentes, a intoxicação alcoólica durante a adolescência é fator de risco para piores desfechos na vida adulta, como o transtorno por uso de substâncias e a piora das funções cognitivas. É possível estudar os impactos do álcool no desenvolvimento em animais de experimentação, que também possuem adolescência e exibem comportamentos homólogos aos dos seres humanos. Desta forma, buscamos avaliar como episódios repetidos de intoxicação alcoólica durante a adolescência podem alterar os comportamentos de avaliação de risco e consumo de etanol na fase adulta. Utilizamos camundongos C57Bl/6 fêmeas e machos com seis semanas de idade que passaram por quatro episódios intermitentes de intoxicação alcoólica (3,2 g/kg à 20% v/v, i.p.) ou administração de salina (0,9% p/v - grupo controle). Em um experimento foi coletado sangue no primeiro e último dia de intoxicação para avaliação da alcoolemia sérica. Nos demais experimentos, os animais, já na fase adulta com mais de oito semanas de idade, foram submetidos a testes comportamentais para avaliação de comportamentos do tipo ansioso com foco na avaliação de risco, com ou sem exposição prévia a uma baixa dose de etanol (1,2 g/kg à 10% v/v, i.p.), ou ao teste de consumo voluntário de etanol. Os animais desenvolveram tolerância ao efeito depressor postural do etanol, apesar de continuarem fortemente intoxicados em todos os dias do protocolo. Na vida adulta, apenas as fêmeas intoxicadas na adolescência apresentaram efeito estimulante e ansiolítico em resposta a uma baixa dose de etanol. Os machos intoxicados apresentaram comportamentos do tipo ansioso, efeito revertido pela administração aguda de uma baixa dose de etanol. Os animais previamente intoxicados fizeram menor avaliação de risco do que os que não haviam recebido etanol na adolescência. As fêmeas intoxicadas consumiram mais etanol na vida adulta do que as fêmeas do grupo controle, efeito não observado nos machos. A análise da microestrutura do consumo oral voluntário revelou que os machos intoxicados demoraram mais para fazer o primeiro bout de etanol no início do experimento, enquanto ao final demoram menos que os machos do grupo controle. Já as fêmeas intoxicadas demoraram mais para fazer a primeira lambida de etanol, porém fizeram mais bouts do que as fêmeas do grupo controle, efeito não observado nos machos. Os dados sugerem que a intoxicação alcoólica pesada durante a adolescência altera os padrões comportamentais do tipo ansioso e de avaliação de risco, além dos níveis de consumo voluntário de etanol na vida adulta com diversidade de efeitos para cada sexo.
Adolescence is the final stage of neurodevelopment and it is during this period that the experimentation with alcohol (or ethanol) usually occurs. It is popular among young people to consume many doses of this drug in a short period of time, which leads to alcoholic intoxication. In addition to greater vulnerability to accidents, alcohol intoxication during adolescence is a risk factor for worse outcomes in adulthood, such as substance use disorder and worsening of cognitive functions. It is possible to study the impacts of alcohol on development in experimental animals, which also have adolescence and similar behaviors to those presented by humans. We sought to assess how repeated episodes of alcohol intoxication during adolescence can alter risk assessment and ethanol consumption behaviors in adulthood. We used C57Bl/6 female and male adolescent mice (six weeks old) exposure to four intermittent episodes of alcohol intoxication (3.2 g/kg at 20% v/v, i.p.) or saline administration (0.9% p/v - control group). In one experiment, blood was collected on the first and last day of intoxication to assess blood alcohol levels. In the other experiments, animals, already in adulthood (eight weeks old), were submitted to behavioral anxiety tests focused on risk assessment, with or without exposure to a low dose of ethanol (1.2 g/kg at 10% v/ v, i.p.), or submitted to an intermittent overnight voluntary ethanol drinking protocol. The animals developed tolerance to the loss of righting reflex induced by ethanol, despite continuing to be heavily intoxicated on all days of the protocol. In adulthood, only female mice intoxicated in adolescence showed a stimulant and anxiolytic-like effect after a low dose of ethanol. Intoxicated males showed anxiety-like behavior, an effect reversed by the acute administration of a low dose of ethanol. Previously intoxicated animals presented less risk-assessment behaviors. Intoxicated females consumed more ethanol in adulthood than control females, an effect not observed in males. The microstructure analysis of voluntary consumption revealed that intoxicated males took longer to present the first ethanol bout at the initial phase of the protocol while at its end they took less time than control males. Meanwhile intoxicated females took longer to do the first ethanol lick but presented more bouts than control females. Our data indicate that heavy alcohol intoxication during adolescence may alter anxiety-type and risk-assessment behavioral patterns, as well as the voluntary ethanol consumption levels in adulthood, with sex-specific effects.
Adolescence is the final stage of neurodevelopment and it is during this period that the experimentation with alcohol (or ethanol) usually occurs. It is popular among young people to consume many doses of this drug in a short period of time, which leads to alcoholic intoxication. In addition to greater vulnerability to accidents, alcohol intoxication during adolescence is a risk factor for worse outcomes in adulthood, such as substance use disorder and worsening of cognitive functions. It is possible to study the impacts of alcohol on development in experimental animals, which also have adolescence and similar behaviors to those presented by humans. We sought to assess how repeated episodes of alcohol intoxication during adolescence can alter risk assessment and ethanol consumption behaviors in adulthood. We used C57Bl/6 female and male adolescent mice (six weeks old) exposure to four intermittent episodes of alcohol intoxication (3.2 g/kg at 20% v/v, i.p.) or saline administration (0.9% p/v - control group). In one experiment, blood was collected on the first and last day of intoxication to assess blood alcohol levels. In the other experiments, animals, already in adulthood (eight weeks old), were submitted to behavioral anxiety tests focused on risk assessment, with or without exposure to a low dose of ethanol (1.2 g/kg at 10% v/ v, i.p.), or submitted to an intermittent overnight voluntary ethanol drinking protocol. The animals developed tolerance to the loss of righting reflex induced by ethanol, despite continuing to be heavily intoxicated on all days of the protocol. In adulthood, only female mice intoxicated in adolescence showed a stimulant and anxiolytic-like effect after a low dose of ethanol. Intoxicated males showed anxiety-like behavior, an effect reversed by the acute administration of a low dose of ethanol. Previously intoxicated animals presented less risk-assessment behaviors. Intoxicated females consumed more ethanol in adulthood than control females, an effect not observed in males. The microstructure analysis of voluntary consumption revealed that intoxicated males took longer to present the first ethanol bout at the initial phase of the protocol while at its end they took less time than control males. Meanwhile intoxicated females took longer to do the first ethanol lick but presented more bouts than control females. Our data indicate that heavy alcohol intoxication during adolescence may alter anxiety-type and risk-assessment behavioral patterns, as well as the voluntary ethanol consumption levels in adulthood, with sex-specific effects.