Dipyrone attenuates acute sickness response to lipopolysaccharide in mice

Soncini, Roseli; Souza, Denise F. de; Neves, A.; Braga, Daniela S.; Andrade, C.A.F.; Giusti‐Paiva, Alexandre

doi:10.1016/j.neulet.2012.03.070

Cited by 19 publications

(19 citation statements)

References 30 publications

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“…This long-lasting effect may have influenced the performance of the animals in the light-dark and forced swim tests, two behavioral assessments with a considerable locomotor component. Usually, studies refer this effect as “depressed locomotor activity” [45, 46]. Thus, it is difficult to dissociate sickness behavior from depressive-like behavior in the present study.…”

Section: Discussionmentioning

confidence: 92%

Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway

et al. 2017

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Recent studies have demonstrated the intimate relationship between depression and immune disturbances. Aware of the efficacy limits of existing antidepressant drugs and the potential anti-inflammatory properties of propentofylline, we sought to evaluate the use of propentofylline as a depression treatment. We used a rat model of depression induced by repetitive lipopolysaccharide (LPS) administrations. We have studied sickness behavior, by assessing daily body weight, open field behavior, and TNF-α plasmatic levels. Anxiety-like behavior (light-dark test), depressive-like behavior (forced swim test), plasmatic levels of the brain-derived neurotrophic factor (BDNF, depression biomarker), and central glial fibrillary acidic protein (GFAP) expression (an astrocyte biomarker) were also evaluated. LPS induced body weight loss, open field behavior impairments (decreased locomotion and rearing, and increased immobility), and increased TNF-α levels in rats, compared with control group. Thus, LPS induced sickness behavior. LPS also increased the immobility and reduced climbing in the forced swim test, when compared with the control group, i.e., LPS induced depressive-like behavior in rats. Propentofylline prevented sickness behavior after four days of consecutive treatment, as well as prevented the depressive-like behavior after five days of consecutive treatments. Propentofylline also prevented the increase in GFAP expression induced by LPS. Neither LPS nor propentofylline has influenced the anxiety and BDNF levels of rats. In conclusion, repetitive LPS administrations induced sickness behavior and depressive-like behavior in rats. Propentofylline prevented both sickness behavior and depressive-like behavior via neuroinflammatory pathway. The present findings may contribute to a better understanding and treatment of depression and associated diseases.

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Section: Discussionmentioning

confidence: 92%

Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway

et al. 2017

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“…Here, LPS administration depressed locomotor activity in the OFT, and pifithrin-μ treatment reversed this effect. The lightdark box test is a characteristic tool used in the assessment of behaviors associated with anxiety [17,18] . Our data showed that LPS elicited an anxiogenic-like response in the light-dark box test, exemplified by a significant increase in the latency to first transition and a significant decrease in the total number of transitions.…”

Section: Discussionmentioning

confidence: 99%

Pifithrin-μ Attenuates Acute Sickness Response to Lipopolysaccharide in C57BL/6J Mice

Zhang¹,

Wang²,

Hu³

et al. 2016

Pharmacology

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Sickness behavior is a coordinated set of behavioral changes that happen as a response to acute infectious pathogens. Its well-known benefit is to reorganize the organism's priorities to cope with infection, but the uncontrolled development of sickness behavior may trigger negative feelings or chronic depressive events. This study aims at investigating the potential effect of pifithrin-μ, an inhibitor of heat shock protein 70 substrate binding activity, on lipopolysaccharide (LPS)-induced sickness response. C57BL/6J mice were submitted to the forced swimming test (FST), tail suspension test (TST), open field test (OFT) and light-dark box test. Food intake and body weight were also evaluated. The serum corticosterone level was measured using an ELISA kit. Treatment of mice with LPS (0.33 mg/kg, i.p.) markedly increased the floating and immobility time in the FST and TST, respectively, and depressed locomotor activity in the OFT. LPS administration prolonged the latency to first transition and reduced the total number of transitions in the light-dark box test. In addition, LPS induced anorexia and increased serum corticosterone levels. Pretreatment with pifithrin-μ (1 or 5 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, OFT and light-dark box test. Pifithrin-μ also prevented the formation of anorexia as well as the increase in serum corticosterone levels in LPS-treated mice. Our previous studies showed that pifithrin-μ prevents the production of pro-inflammatory factors in both microglia and macrophages. These findings presented here extend the role of pifithrin-μ beyond an anti-inflammatory molecule to a modulator of sickness behavior.

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“…Of note, a recent study demonstrated that acute oral administration of high doses of the analgesic agent dipyrone displayed antidepressant-like effects in the mouse model of acute inflammation elicited by LPS [32]. Additionally, a recent publication showed a clear relationship between chronic pain and depression, in a rat model of inflammatory arthritis elicited by the intra-articular injection of CFA, via mechanisms involving the upregulation of IDO [17].…”

Section: Discussionmentioning

confidence: 99%

“…Independent groups were used to analyse the effects of anti-inflammatory or antidepressant drugs on paw edema or depression-like behavior. The schedules of treatment were determined on the basis of previous literature or on pilot experiments [15,31,32,33,34]. …”

Section: Methodsmentioning

confidence: 99%

Synergistic Effects of Celecoxib and Bupropion in a Model of Chronic Inflammation-Related Depression in Mice

et al. 2013

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This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund’s Adjuvant (CFA). Male Swiss mice received an intraplantar (i.pl.) injection of CFA (50 µl/paw) or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks), and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST) or forced-swimming (FST) depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg), fluoxetine (20 mg/kg) and bupropion (30 mg/kg) significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg), indomethacin (10 mg/kg) and celecoxib (30 mg/kg) markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg) or pregabalin (30 mg/kg) significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg) did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg) was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg), and depression behaviour was prevented by celecoxib (30 mg/kg). The co-treatment with bupropion and celecoxib (3 mg/kg each) significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and anti-inflammatory agents bupropion and celecoxib might represent an attractive therapeutic strategy for depression.

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Dipyrone attenuates acute sickness response to lipopolysaccharide in mice

Cited by 19 publications

References 30 publications

Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway

Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway

Pifithrin-μ Attenuates Acute Sickness Response to Lipopolysaccharide in C57BL/6J Mice

Synergistic Effects of Celecoxib and Bupropion in a Model of Chronic Inflammation-Related Depression in Mice

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