Enhanced cholinergic-tone during the stress induce a depressive-like state in mice.

Major depressive disorder has a heterogeneous etiology, since it arises from the interaction of multiple factors and different pathophysiological mechanisms are involved in the symptomatology. This study aimed to investigate the role of the cholinergic system in the susceptibility to stress and, consequently, in the depression-like behavior. C57BL/6 mice were treated with Physostigmine (PHYS), an acetylcholinesterase (AChE) inhibitor, and were submitted to the social defeat stress. For the behavioral evaluation of the locomotor activity, anxiety-like and depression-like behaviors the open field, elevated plus maze, sucrose preference, social interaction and forced swim were used. Hippocampus and prefrontal cortex samples were collected for evaluation of AChE activity, as well as blood samples for analysis of serum cortisol levels. Our results showed that 15 min after the injection of PHYS there was a significant inhibition of AChE activity in the hippocampus and in the prefrontal cortex. On the other hand, in the end of the experimental design, day 12, there was no difference in AChE activity levels. Inhibition of AChE and exposure to the stress led to an increase in cortisol levels. Animals that received PHYS and were exposed to stress showed less social interaction and greater learned helplessness, anhedonia and anxious-like behavior. Taken together, our findings suggest that increasing the cholinergic tone shortly before stress induction impacts on the ability to cope with upcoming stressful situations, leading to a depressive-like state.

O efeito dos anestésicos inalatórios halotano e sevoflurano em um modelo experimental de lesão hepática / Effects of the inhalational anesthetics halothane and sevoflurane on an experimental model of hepatic injury

JUSTIFICATIVA E OBJETIVOS: A lesão hepática pós-anestesia inalatória ainda é controversa. Estudos sugerem que agentes inalatórios geram uma resposta imune que pode provocar lesões hepáticas. O objetivo deste estudo é analisar o efeito dos anestésicos inalatórios halotano e sevoflurano no fígado de ratos submetidos à hipóxia e à reperfusão. MÉTODO: Foram utilizados 30 ratos Wistar pré-tratados com fenobarbital 0,1 por cento por cinco dias, com suspensão da medicação 24 horas antes do experimento, a fim de provocar a lesão hepática. Os animais foram distribuídos em cinco grupos com seis ratos cada. O Grupo C foi o de controle, sem qualquer tipo de tratamento; o Grupo F foi aquele no qual se induziu lesão hepática com fenobarbital; o Grupo Hipóxia foi exposto a 14 por cento de oxigênio (O2); o Grupo H recebeu halotano 1 por cento e 14 por cento de O2; e o Grupo S recebeu sevoflurano 2 por cento e 14 por cento de O2. Contadas 24 horas após a exposição dos gases, realizaram-se coletas de sangue para avaliação de transaminases (AST e ALT) e de amostras de fígado para avaliação histológica. Foram usados os testes de Análise de Variância não paramétrica de Kruskal-Wallis e, para comparação de médias, os testes de Newman-Keuls. RESULTADOS: A atividade enzimática revelou que os valores de média amostral de AST (280,33 para halotano, 181 para sevoflurano) e ALT (235 para halotano e 48,33 para sevoflurano) não indicaram diferença estatística significativa; os grupos testados apresentaram valores elevados. O sevoflurano, quando comparado com o halotano à microscopia óptica, apresentou índices menores de alteração morfológica, com p = 0,045 para esteatose, p = 0,0075 para infiltrado inflamatório e p = 0,0074 para necrose. CONCLUSÕES: O Grupo sevoflurano, quando comparado ao Grupo halotano, não apresentou lesão no parênquima hepático quando avaliado por microscopia óptica.

BACKGROUND AND OBJECTIVES: Hepatic injury after inhalational anesthesia is controversial. Studies have suggested that inhalational agents generate an immune response that can provoke hepatic injury. The objective of this study was to analyze the effects of the inhalational agents halothane and sevoflurane on the liver of rats submitted to hypoxia and reperfusion. METHODS: Thirty Wistar rats, pretreated with 0.1 percent phenobarbital for 5 days, with discontinuation of the drug 24 hours before the experiment to cause hepatic injury, were used. Animals were distributed in five groups of six rats each. The control group (C) did not receive any treatment; in the F group, phenobarbital was used to induce hepatic injury; the Hypoxia group was submitted to 14 percent oxygen (O2); the H group received 1 percent halothane and 14 percent O2; and the S group received 2 percent sevoflurane and 14 percent O2. Twenty-four hours after exposure to the gases, blood samples were collected to evaluate transaminases (AST and ALT), and liver samples were collected for histological evaluation. Kruskal-Wallis Analysis of Variance and the Newman-Keuls test were used. RESULTS: Enzymatic activity mean values of AST (280.33, for halothane, 181, for sevoflurane) and ALT (235 for halothane, and 48.33, for sevoflurane) did not show significant differences, and all groups showed elevated values. Compared to halothane on optical microscopy, sevoflurane had lower indices of morphologic changes with p = 0.045, for steatosis, p = 0.0075, for inflammatory infiltrate, and p = 0.0074, for necrosis. CONCLUSIONS: Compared to the halothane group, sevoflurane did not show injuries of the liver parenchyma on optical microscopy.

JUSTIFICATIVA Y OBJETIVOS: La lesión hepática postanestesia inhalatoria todavía es algo controversial. Algunos estudios sugieren que los agentes inhalatorios generan una respuesta inmune que puede provocar lesiones hepáticas. El objetivo de este estudio fue analizar el efecto de los anestésicos inhalatorios halotano y sevoflurano en el hígado de ratones que fueron sometidos a la hipoxia y a la reperfusión. MÉTODO: Fueron utilizados 30 ratones Wistar tratados previamente con fenobarbital al 0,1 por ciento durante cinco días, con suspensión de la medicación 24 horas antes del experimento para provocar la lesión hepática. Los animales fueron distribuidos en cinco grupos con seis ratones cada uno. El grupo C fue el de control, sin ningún tipo de tratamiento; el grupo F fue aquel en el cual se indujo la lesión hepática con fenobarbital; el grupo Hipoxia se expuso a un 14 por ciento de oxígeno (O2); el grupo H recibió halotano al 1 por ciento y al 14 por ciento de O2; y el grupo S recibió sevoflurano al 2 por ciento y al 14 por ciento de O2. Contadas 24 horas después de la exposición de los gases, se realizó la recolección de sangre para la evaluación de las transaminasas (AST y ALT), y de las muestras de hígado para la evaluación histológica. Fueron usados los test de Análisis de Variancia no paramétrica de Kruskal-Wallis, y para la comparación de los promedios se usaron los test de Newman-Keuls. RESULTADOS: La actividad enzimática arrojó valores de promedio de muestra de AST (280,33 para halotano, 181 para sevoflurano y ALT 235 para halotano y 48,33 para sevoflurano), que no indicaron diferencia estadística significativa: los grupos testados presentaron valores elevados. El sevoflurano, cuando fue comparado con el halotano a la microscopía óptica, presentó índices menores de alteración morfológica, con p = 0,045 para esteatosis, p = 0,0075 para infiltrado inflamatorio y p = 0,0074 para necrosis. CONCLUSIONES: El grupo sevoflurano, cuando se comparó con el grupo h...

Effects of the inhalational anesthetics halothane and sevoflurane on an experimental model of hepatic injury.

BACKGROUND AND OBJECTIVES: Hepatic injury after inhalational anesthesia is controversial. Studies have suggested that inhalational agents generate an immune response that can provoke hepatic injury. The objective of this study was to analyze the effects of the inhalational agents halothane and sevoflurane on the liver of rats submitted to hypoxia and reperfusion. METHODS: Thirty Wistar rats, pretreated with 0.1% phenobarbital for 5 days, with discontinuation of the drug 24 hours before the experiment to cause hepatic injury, were used. Animals were distributed in five groups of six rats each. The control group (C) did not receive any treatment; in the F group, phenobarbital was used to induce hepatic injury; the Hypoxia group was submitted to 14% oxygen (O(2)); the H group received 1% halothane and 14% O(2); and the S group received 2% sevoflurane and 14% O(2). Twenty-four hours after exposure to the gases, blood samples were collected to evaluate transaminases (AST and ALT), and liver samples were collected for histological evaluation. Kruskal-Wallis Analysis of Variance and the Newman-Keuls test were used. RESULTS: Enzymatic activity mean values of AST (280.33, for halothane, 181, for sevoflurane) and ALT (235 for halothane, and 48.33, for sevoflurane) did not show significant differences, and all groups showed elevated values. Compared to halothane on optical microscopy, sevoflurane had lower indices of morphologic changes with p=0.045, for steatosis, p=0.0075, for inflammatory infiltrate, and p=0.0074, for necrosis. CONCLUSIONS: Compared to the halothane group, sevoflurane did not show injuries of the liver parenchyma on optical microscopy.