Attenuation of the levels of pro-inflammatory cytokines prevents depressive-like behavior during ethanol withdrawal in mice

Fraga-Junior, E.B.; Fernandes, Isadora Luiza; Rohden, Christopher Alecsander Herane; Doneda, Diego Luiz; Ynoue, H.N.; Rios-Santos, Fabrício; Lima, Edson Alves de; Buss, Z; Vandresen-Filho, Samuel

doi:10.1016/j.brainresbull.2022.10.014

Cited by 7 publications

(6 citation statements)

References 87 publications

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“…On the contrary, Liu et al 46 and Yang et al 47 reported an increase in the levels of TNF-α in serum and hippocampus when the rats were exposed to chronic mild stress. In the same line, Gómez and Fraga-Junior 45,32 reported an increase in serum and hippocampus levels of TNF-α in rats following ethanol administration respectively. Possibly by the time the samples were harvested, an insignificant amount of TNF-α had been released both in the serum and hippocampus.…”

Section: Discussionmentioning

confidence: 76%

“…External stress was induced in groups II - IV using FST as elaborately explained by Fraga-Junior. 32 Briefly, FST was done by immersing rats individually in a transparent bucket (30 cm in diameter × 60 cm high) containing water (25°C) to a depth of 20 cm from which they couldn’t escape and couldn’t touch the bottom. The induction process was done in two sessions, the first session was done for 15 min, and the second session was done after 24 h, for five minutes.…”

Section: Methodsmentioning

confidence: 99%

“…Ethanolinduced DLB. Ethanol-induced DLB model as elaborately explained by Kesic and Fraga-Junior 32,33 was used for this model. Briefly, ethanol (0.07 g/kg) was injected to the rats intraperitoneally and 30 min after the administration, they were anesthetized using 60 mg/kg of sodium pentobarbital, also intraperitoneally, and then placed in the stereotaxic frame.…”

Section: Methodsmentioning

confidence: 99%

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Fluoxetine attenuates stress-induced depression-like behavior due to decrease in pro-inflammatory cytokines in male rats

Nabirumbi,

Onohuean,

Drago

et al. 2024

Science Progress

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Background: Pro-inflammatory cytokines are implicated in depression caused by both environmental- and alcohol-induced stress. The purpose of the study was to investigate the cytokine levels in serum and hippocampus following induction of depression-like behaviors (DLB) by either forced swimming test (FST) or ethanol-induced DLB (EID). We also investigated the effect of prior administration of antidepressant drug fluoxetine on cytokines in animals exposed to both models of DLB. Methods: Animals were pretreated with fluoxetine before inducing DLB, while DLB was induced in some animals using FST and ethanol in different groups of rats without fluoxetine pretreatment. The ELISA was used to detect changes in cytokine (IL-1β, IL-6, and TNF-α) levels in serum and hippocampus. Results: The mean levels of IL-1β and IL-6 measured in serum and hippocampus were significantly higher in FST and EID models when compared to the control group. The serum concentrations of IL-1β and IL-6 were significantly reduced in animals pre-treated with 5 mg/kg and 10 mg/kg of fluoxetine in both FST and EID models when compared to the untreated FST and EID groups respectively. Conclusions: In conclusion, both environment and alcohol can induce stress and DLB in rats with similar intensity, and their mechanisms of DLB induction involve activation of pro-inflammatory cytokines. Moreover, fluoxetine can prevent stress-induced inflammation in models of DLB.

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Section: Discussionmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Fluoxetine attenuates stress-induced depression-like behavior due to decrease in pro-inflammatory cytokines in male rats

Nabirumbi,

Onohuean,

Drago

et al. 2024

Science Progress

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“…In behavioral studies, the authors showed that a STAT3 antagonist blocked both the chronic alcohol activation of STAT3 and sucrose preference, which was used as a behavioral measure of anhedonia, a cluster of well-known negative affect behavioral symptoms associated with alcohol withdrawal, thereby linking STAT3 with the behavioral effects of alcohol [ 29 ]. Recent studies have also linked increased levels of proinflammatory cytokines, including IL-6, during withdrawal from chronic alcohol (14 days of ethanol by gavage, 19 days of withdrawal) as important factors in depressive-like behaviors associated with alcohol abstinence [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

“…This effect of alcohol exposure/abstinence may contribute to the reduced immobility (forced swim test) in the 2BC-CIE-treated mice compared to the 2BC mice, which is indicative of reduced depressive-like behavior. Recent studies showed that withdrawal from chronic alcohol increased depressive-like behaviors (forced swim test and tail suspension test) in mice, an effect associated with an increase in the brain levels of TNF-α, IL-1β, and IL-6 [ 90 ]. Blocking the increased expression of the proinflammatory cytokines also blocked the depressive-like behavior [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure

Gruol,

Calderon,

Huitron-Resendiz

et al. 2023

Cells

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Alcohol consumption activates the neuroimmune system of the brain, a system in which brain astrocytes and microglia play dominant roles. These glial cells normally produce low levels of neuroimmune factors, which are important signaling factors and regulators of brain function. Alcohol activation of the neuroimmune system is known to dysregulate the production of neuroimmune factors, such as the cytokine IL-6, thereby changing the neuroimmune status of the brain, which could impact the actions of alcohol. The consequences of neuroimmune–alcohol interactions are not fully known. In the current studies we investigated this issue in transgenic (TG) mice with altered neuroimmune status relative to IL-6. The TG mice express elevated levels of astrocyte-produced IL-6, a condition known to occur with alcohol exposure. Standard behavioral tests of alcohol drinking and negative affect/emotionality were carried out in homozygous and heterozygous TG mice and control mice to assess the impact of neuroimmune status on the actions of chronic intermittent alcohol (ethanol) (CIE) exposure on these behaviors. The expressions of signal transduction and synaptic proteins were also assessed by Western blot to identify the impact of alcohol–neuroimmune interactions on brain neurochemistry. The results from these studies show that neuroimmune status with respect to IL-6 significantly impacts the effects of alcohol on multiple levels.

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Ascorbic acid supplementation in adolescent rats ameliorates anxiety‐like and depressive‐like manifestations of nicotine‐ethanol abstinence: Role of oxidative stress, inflammatory, and serotonergic mechanisms

Najafzadeh,

Mahdizadeh,

Kakhki

et al. 2024

Intl J of Devlp Neuroscience

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BackgroundThe present study aims to assess the therapeutic potential of vitamin C (Vit C) on anxiety‐ and depressive‐like behavior induced by abstinence from chronic nicotine‐ethanol co‐exposure in adolescent male rats.Materials and methodsAdolescent male rats were divided into seven experimental groups with ten rats as follows: 1) vehicle, 2) Nicotine (Nic)‐Ethanol (Eth): received Nic (2 mg/kg) and Eth (20%) in drinking water from 21 to 42 days of age, 3–5) Nic‐Eth‐Vit C 100/200/400: received Nic and Eth from 21 to 42 days of age and received Vit C 100/200/400 mg/kg from 43 to 63 days of age, 6) Nic‐Eth‐Bupropion (Bup)‐ Naloxone (Nal): received Nic and Eth from 21 to 42 days of age and received Bup and Nal from 43 to 63 days of age, and 7) Vit C 400 mg/kg: received Vit C 400 mg/kg from 43 to 63 days of age. Behavioral assessments were done by elevated plus maze (EPM), forced swimming test (FST), marble burring test (MBT), and open field tests (OFT). Furthermore, specific biochemical variables associated with oxidative, inflammatory, and serotonergic profiles were quantified.ResultsAccording to the obtained results, Nic and Eth induced anxiety and depression in treated rats. We showed that two higher doses of Vit C increases the active struggling time in FST and decreases both the time spent in the peripheral zone of OFT and the time spent in the closed arms of EPM. In addition, animals treated by Vit C buried less number of marbles in MBT compared to their control counterparts. Nic and Eth induced oxidative stress and inflammation in cortical tissues of treated rats. Biochemical parameters were improved in the Nic‐Eth group receiving Vit C 200/400 mg/kg and Bup‐Nal through establishing a balance between oxidant/anti‐oxidant and inflammatory/anti‐inflammatory mediators. In addition, serotonin level was increased, while Monoamine oxidase (MAO) activity was notably decreased.ConclusionThe present findings support the beneficial effect of Vit C on anxiety‐ and depressive‐like behavior induced by Nic‐Eth withdrawal through various mechanisms such as the promotion of antioxidant defense, suppression of inflammatory mediators, and enhancement of serotoninergic function.

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Attenuation of the levels of pro-inflammatory cytokines prevents depressive-like behavior during ethanol withdrawal in mice

Cited by 7 publications

References 87 publications

Fluoxetine attenuates stress-induced depression-like behavior due to decrease in pro-inflammatory cytokines in male rats

Fluoxetine attenuates stress-induced depression-like behavior due to decrease in pro-inflammatory cytokines in male rats

Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure

Ascorbic acid supplementation in adolescent rats ameliorates anxiety‐like and depressive‐like manifestations of nicotine‐ethanol abstinence: Role of oxidative stress, inflammatory, and serotonergic mechanisms

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