Imipramine reverses the depressive symptoms in sepsis survivor rats

Tuon, Lisiane; Comim, Clarissa M.; Antunes, Moises M.; Constantino, Larissa; Machado, Roberta; Izquierdo, Iván; Quevedo, Joao L De; Dal‐Pizzol, Felipe

doi:10.1007/s00134-007-0804-y

Cited by 23 publications

(19 citation statements)

References 10 publications

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“…The depressive symptoms evaluated by forced swimming task were reversed after imipramine administration. Our data provided evidence that CLP-induced depressive symptoms are sensitive to antidepressants [91].…”

Section: Depressive-like Symptoms and Anxiety-like Behaviorsupporting

confidence: 55%

The Septic Brain

et al. 2008

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Sepsis is a major disease entity with important clinical implications. Sepsis-induced multiple organ failure is associated with a high mortality rate in humans and is clinically characterized by pulmonary, cardiovascular, renal and gastrointestinal dysfunction. Recently, several studies have demonstrated that sepsis survivors present long-term cognitive impairment, including alterations in memory, attention, concentration and/or global loss of cognitive function. However, the pathogenesis and natural history of septic encephalopathy and cognitive impairment are still poorly known and further understanding of these processes is necessary for the development of effective preventive and therapeutic interventions. This review discusses the clinical presentation and underlying pathophysiology of the encephalopathy and cognitive impairment associated with sepsis.

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Section: Depressive-like Symptoms and Anxiety-like Behaviorsupporting

confidence: 55%

The Septic Brain

et al. 2008

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“…The animals were subjected to CLP as previously described (Ritter et al 2003;Tuon et al 2007Tuon et al , 2008Comim et al 2008). Briefly, 74 rats (44 rats were subjected to CLP and 30 to Sham) were anesthetized with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg) administered i.p.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, some reports have shown that sepsis survivor rats have symptoms of depression in the forced swimming task (Tuon et al 2008). Additionally, depressive-like behavior observed 10 days after cecal ligation and perforation (CLP) is reversed by classical antidepressant agent: imipramine (Tuon et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Depressive-Like Parameters in Sepsis Survivor Rats

et al. 2009

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The inflammatory and immune responses evoked in sepsis may create not only an acute brain dysfunction, which occurs in the majority of septic patients, but also long-term deficits such as memory impairment. In this context, we evaluated depressive-like parameters in sepsis survivor rats. For this purpose, male Wistar rats, weighing 300-350 g, underwent cecal ligation and perforation (CLP) (sepsis group) followed by "basic support", or were sham-operated (control group). After 3 days of the sepsis procedure, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). The consumption of sweet food was measured for 7 days (days 10-17) and the body weight was measured before CLP, 10, and 17 days after CLP. Seventeen days after sepsis (immediately after sweet food consumption measurement), the animals were anesthetized and blood was withdrawn for the analyses of corticosterone and adrenocorticotropic hormone (ACTH) levels, and immediately killed by decapitation. The adrenal gland and hippocampus were immediately isolated and weighed, and the hippocampus was utilized for determining brain-derived neurotrophic factor (BDNF) levels. It was observed that animals subjected to CLP presented decreased sucrose intake. Septic rats did not increase body weight and presented an increase in the weight of adrenal gland. Both corticosterone and ACTH levels were increased, while hippocampus weight and BDNF levels in the hippocampus decreased. The treatment with imipramine reversed all the parameters described above. Our results supported the hypothesis that rats that survive sepsis show depressive-like behavior, alterations in the hypothalamus-pituitary-adrenal axis, and decreased BDNF levels in the hippocampus.

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“…Imipramine, a standard antidepressant, was obtained from Novartis Pharmaceutical Industry (São Paulo, Brazil), and a dose of 10 mg/kg was injected intraperitoneally (i.p.) once a day over 21 days (Tuon et al 2007). Twelve hours after the last injection of BCAA, the animals were submitted to behavioral testing.…”

Section: Animalsmentioning

confidence: 99%

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

et al. 2013

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Maple syrup urine disease (MSUD) is an inborn metabolism error caused by a deficiency of branched-chain a-keto acid dehydrogenase complex activity. This blockage leads to an accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their corresponding a-keto and a-hydroxy acids. Previous reports suggest that MSUD patients are at high risk for chronic neuropsychiatric problems. Therefore, in this study, we assessed variables that suggest depressive-like symptoms (anhedonia as measured by sucrose intake, immobility during the forced swimming test and body and adrenal gland weight) in rats submitted to chronic administration of BCAA during development. Furthermore, we determined if these parameters were sensitive to imipramine and N-acetylcysteine/deferoxamine (NAC/DFX). Our results demonstrated that animals subjected to chronic administration of branched-chain amino acids showed a decrease in sucrose intake without significant changes in body weight. We also observed an increase in adrenal gland weight and immobility time during the forced swimming test. However, treatment with imipramine and NAC/DFX reversed these changes in the behavioral tasks. In conclusion, this study demonstrates a link between MSUD and depression in rats. Moreover, this investigation reveals that the antidepressant action of NAC/DFX and imipramine might be associated with their capability to maintain pro-/anti-oxidative homeostasis.

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Imipramine reverses the depressive symptoms in sepsis survivor rats

Abstract: The depressive symptoms evaluated by forced swimming test had been reversed after imipramine administration. Our data provide evidence that CLP-induced depressive symptoms are sensitive to antidepressants.

Cited by 23 publications

References 10 publications

The Septic Brain

The Septic Brain

Depressive-Like Parameters in Sepsis Survivor Rats

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

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