Etanol e cafeína: impactos no consumo voluntário e na estimulação locomotora de camundongos
Data
2023-11-10
Autores
Borges, Beatriz de Petribu da Costa Nunes 
Orientadores
Formigoni, Maria Lucia Oliveira de Souza
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: O aumento do consumo combinado de bebidas alcoólicas e energéticas, cujo principal componente é a cafeína, tem despertado preocupação, dada a limitação de informações sobre os efeitos da interação destas substâncias. Estudos controlados, com animais de laboratório, podem contribuir para ampliar o conhecimento sobre os efeitos farmacológicos e comportamentais da administração combinada de EtOH e cafeína. Objetivos: Avaliar a influência do etanol e/ou cafeína e do tipo de pré-exposição (intraperitoneal (i.p.) ou consumo voluntário) na expressão do efeito estimulante da locomoção de camundongos Swiss. Métodos: No experimento i.p., os animais receberam salina, EtOH (1,9 g/kg), cafeína (6 mg/kg) ou EtOH + cafeína por 21 dias consecutivos e, semanalmente, a locomoção foi mensurada por 15 minutos, imediatamente após a administração. Duas semanas após o final do protocolo, os animais receberam administrações agudas (desafios) de salina, EtOH, cafeína e EtOH + cafeína, com intervalo de 2 ou 3 dias entre elas, sendo sua locomoção mensurada por 15 minutos. Os animais foram classificados em subgrupos, definidos a partir da intensidade da locomoção no desafio com EtOH considerando três tercis (superior: alta locomoção (AL); intermediário: média locomoção (ML) e inferior: baixa locomoção (BL)). No protocolo IOD (Intermittent Overnight Drinking), os camundongos foram alocados em caixas com dois licômetros, um contendo água e o outro uma das substâncias de teste: EtOH (10% v/v), cafeína (0,75 mg/ml) ou EtOH + cafeína. O protocolo consistia na exposição aos licômetros por 16 h no período escuro (das 17 h às 9 h do dia seguinte), em 12 noites intercaladas. Duas semanas após a última exposição às drogas, os camundongos foram submetidos a desafios idênticos aos do experimento com administração i.p. Resultados: A administração isolada de EtOH ou cafeína não provocou estimulação agudo a locomoção (dia 1 do tratamento). Após 21 dias de tratamento, somente o
grupo que recebeu EtOH + cafeína apresentou sensibilização (atividade significativamente maior que no dia 1). No desafio em que todos os grupos receberam EtOH, sem considerar a classificação em subgrupos, os animais do grupo tratado com EtOH + cafeína apresentaram maior atividade do que os tratados com salina e do que eles mesmos no desafio salina. Na mesma ocasião, o grupo tratado com EtOH apresentou maior locomoção do que no desafio salina. No desafio com EtOH + cafeína os grupos tratados com EtOH, cafeína e EtOH + cafeína apresentaram maior locomoção do que nos desafios com salina e etanol, indicando que a cafeína potencializou o efeito estimulante. Entretanto, isso não foi observado em todos os animais pois considerando a classificação, no desafio com EtOH + cafeína
observamos efeito estimulante nos subgrupos de animais pré-tratados com EtOH (AL e ML), cafeína (AL) e EtOH + cafeína (AL, ML e BL). No protocolo IOD, observamos que a solução de EtOH foi aversiva, pois a preferência por água foi maior do que pelas soluções contendo EtOH. O consumo médio diário de EtOH foi cerca de 1,6 g/kg, o de EtOH + cafeína de 1,4 g/kg de EtOH e 13mg/kg de cafeína e o de cafeína isolada de 43 mg/kg. Nos desafios após o protocolo IOD, observamos efeitos significativos somente quando classificamos os animais em subgrupos. No desafio com EtOH observamos efeito estimulante nos subgrupos cafeína AL e EtOH + cafeína AL. O desafio com a mistura de EtOH + cafeína induziu efeito estimulante no grupo que consumia somente água e nos subgrupos EtOH AL, cafeína AL e EtOH + cafeína AL. Conclusões: A cafeína em combinação com EtOH intensifica o efeito estimulante da
locomoção, em comparação aos efeitos dessas duas drogas que isoladamente, não produziram estimulação locomotora na primeira administração. A administração crônica i.p. produziu efeitos mais intensos do que o consumo oral, havendo significativa variabilidade individual na expressão de respostas sensibilizadas, que foram mais robustas nos subgrupos classificados no desafio com Etanol como AL.
Introduction: The increase in the combined consumption of alcoholic and energy drinks, the main component of which is caffeine, has caused concern, given the limited information on the effects of the interaction between these substances. Controlled studies with laboratory animals can contribute to expanding knowledge about the pharmacological and behavioral effects of the combined administration of EtOH and/or caffeine. Objectives: To evaluate the influence of the combination of ethanol and caffeine and the type of pre-exposure (intraperitoneal (i.p.) or voluntary consumption) on the expression of the locomotion-stimulating effect in Swiss mice. Methods: In the i.p. experiment, the animals received saline, EtOH (1.9 g/kg), caffeine (6 mg/kg) or EtOH + caffeine for 21 consecutive days and locomotion was measured weekly for 15 minutes immediately after administration. Two weeks after the end of the protocol, the animals received acute administrations (challenges) of saline, EtOH, caffeine and EtOH + caffeine, with an interval of 2 or 3 days between them, and their locomotion was measured for 15 minutes. The animals were classified into subgroups based on the intensity of locomotion in the EtOH challenge, considering three terciles (top: high locomotion (HL); middle: medium locomotion (ML) and bottom: low locomotion (LL)). In the IOD (Intermittent Overnight Drinking) protocol, the mice were placed in boxes with two lickometers, one containing water and the other one of the test substances: EtOH (10% v/v), caffeine (0.75 mg/ml) or EtOH + caffeine. The protocol consisted of exposure to the lickometers for 16 hours in the dark (from 5 pm to 9 am the next day), on 12 alternate nights. Two weeks after the last exposure to the drugs, the mice were subjected to challenges identical to those in the experiment with i.p. administration. Results: The administration of EtOH or caffeine alone did not cause acute stimulation of locomotion (day 1 of treatment). After 21 days of treatment, only the group that received EtOH + caffeine showed sensitization (significantly higher activity than on day 1). In the challenge in which all groups received EtOH, without considering the classification into subgroups, the animals in the group treated with EtOH + caffeine showed higher activity than those treated with saline, and than themselves in the saline challenge. On the same occasion, the group treated with EtOH showed higher locomotion than in the saline challenge. In the challenge with EtOH + caffeine, the groups treated with EtOH, caffeine and EtOH + caffeine showed higher locomotion than in the challenges with saline and ethanol, indicating that caffeine potentiated the stimulant effect. However, this was not observed in all the animals, because considering the classification, in the challenge with EtOH + caffeine we observed a stimulant effect in the subgroups of animals pre-treated with EtOH (HL and ML), caffeine (HL) and EtOH + caffeine (HL, ML and LL). In the IOD protocol, we observed that the EtOH solution was aversive, as the preference for water was higher than for solutions containing EtOH. The average daily consumption of EtOH was around 1.6 g/kg, that of EtOH + caffeine 1.4 g/kg of EtOH and 13mg/kg of caffeine and that of caffeine alone 43 mg/kg. In the challenges after the IOD protocol, we only observed significant effects when we classified the animals into subgroups. In the challenge with EtOH, we observed a stimulant effect in the caffeine HL and EtOH + caffeine HL subgroups. The challenge with a mixture of EtOH + caffeine induced a stimulant effect in the group that consumed only water and in the EtOH HL, caffeine HL and EtOH + caffeine HL subgroups. Conclusions: Caffeine in combination with EtOH intensifies the stimulant effect of locomotion, compared to the effects of these two drugs alone, which did not produce locomotor stimulation in the first administration. Chronic i.p. administration produced more intense effects than oral consumption, and there was significant individual variability in the expression of sensitized responses, which were more robust in the subgroups classified in the challenge with Ethanol as high locomotion.
Introduction: The increase in the combined consumption of alcoholic and energy drinks, the main component of which is caffeine, has caused concern, given the limited information on the effects of the interaction between these substances. Controlled studies with laboratory animals can contribute to expanding knowledge about the pharmacological and behavioral effects of the combined administration of EtOH and/or caffeine. Objectives: To evaluate the influence of the combination of ethanol and caffeine and the type of pre-exposure (intraperitoneal (i.p.) or voluntary consumption) on the expression of the locomotion-stimulating effect in Swiss mice. Methods: In the i.p. experiment, the animals received saline, EtOH (1.9 g/kg), caffeine (6 mg/kg) or EtOH + caffeine for 21 consecutive days and locomotion was measured weekly for 15 minutes immediately after administration. Two weeks after the end of the protocol, the animals received acute administrations (challenges) of saline, EtOH, caffeine and EtOH + caffeine, with an interval of 2 or 3 days between them, and their locomotion was measured for 15 minutes. The animals were classified into subgroups based on the intensity of locomotion in the EtOH challenge, considering three terciles (top: high locomotion (HL); middle: medium locomotion (ML) and bottom: low locomotion (LL)). In the IOD (Intermittent Overnight Drinking) protocol, the mice were placed in boxes with two lickometers, one containing water and the other one of the test substances: EtOH (10% v/v), caffeine (0.75 mg/ml) or EtOH + caffeine. The protocol consisted of exposure to the lickometers for 16 hours in the dark (from 5 pm to 9 am the next day), on 12 alternate nights. Two weeks after the last exposure to the drugs, the mice were subjected to challenges identical to those in the experiment with i.p. administration. Results: The administration of EtOH or caffeine alone did not cause acute stimulation of locomotion (day 1 of treatment). After 21 days of treatment, only the group that received EtOH + caffeine showed sensitization (significantly higher activity than on day 1). In the challenge in which all groups received EtOH, without considering the classification into subgroups, the animals in the group treated with EtOH + caffeine showed higher activity than those treated with saline, and than themselves in the saline challenge. On the same occasion, the group treated with EtOH showed higher locomotion than in the saline challenge. In the challenge with EtOH + caffeine, the groups treated with EtOH, caffeine and EtOH + caffeine showed higher locomotion than in the challenges with saline and ethanol, indicating that caffeine potentiated the stimulant effect. However, this was not observed in all the animals, because considering the classification, in the challenge with EtOH + caffeine we observed a stimulant effect in the subgroups of animals pre-treated with EtOH (HL and ML), caffeine (HL) and EtOH + caffeine (HL, ML and LL). In the IOD protocol, we observed that the EtOH solution was aversive, as the preference for water was higher than for solutions containing EtOH. The average daily consumption of EtOH was around 1.6 g/kg, that of EtOH + caffeine 1.4 g/kg of EtOH and 13mg/kg of caffeine and that of caffeine alone 43 mg/kg. In the challenges after the IOD protocol, we only observed significant effects when we classified the animals into subgroups. In the challenge with EtOH, we observed a stimulant effect in the caffeine HL and EtOH + caffeine HL subgroups. The challenge with a mixture of EtOH + caffeine induced a stimulant effect in the group that consumed only water and in the EtOH HL, caffeine HL and EtOH + caffeine HL subgroups. Conclusions: Caffeine in combination with EtOH intensifies the stimulant effect of locomotion, compared to the effects of these two drugs alone, which did not produce locomotor stimulation in the first administration. Chronic i.p. administration produced more intense effects than oral consumption, and there was significant individual variability in the expression of sensitized responses, which were more robust in the subgroups classified in the challenge with Ethanol as high locomotion.
Descrição
Citação
PETRIBU, Beatriz Nunes. Etanol e cafeína: impactos no consumo voluntário e na estimulação locomotora de camundongos. 2023. 74 f. Tese (Mestrado em Psicobiologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo, 2023.