Protective Effects of Fluoxetine on Decompression Sickness in Mice

Blatteau, Jean-Éric; Barre, S.; Pascual, Aurélie; Castagna, Olivier; Abraini, Jacques H.; Risso, Jean-Jacques; Vallée, Nicolas

doi:10.1371/journal.pone.0049069

Cited by 21 publications

(25 citation statements)

References 31 publications

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“…Specifically, either FLU or DES treatments has shown to decrease the serum level of IL-1β (refs 73 , 74 , 75 , 76 , 77 ) and IL-6. 78 , 79 , 80 , 81 , 82 To the best of our knowledge, our results are the first to show anti-inflammatory effect of MPH and especially, the effect of the combined treatment of DES+MPH. However, there is a need for more studies to establish the exact mechanisms that are responsible for the immunoregulatory effects of chronic use of both antidepressants and MPH.…”

Section: Discussionsupporting

confidence: 51%

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model

et al. 2014

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Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the most common and effective drug treatment for ADHD, thus we aimed to investigate the effects of MPH treatment, by itself or in combination with the antidepressants fluoxetine (FLU) or desipramine (DES). We modified an animal model of PTSD by exposing rats to chronic stress and evaluating the subsequent development of behavioral PTSD-like symptoms, as well as the effects on proinflammatory cytokines, which were implicated in PTSD. We report that while FLU or DES had a beneficial effect on avoidance and hyperarousal symptoms, MPH improved all three symptoms. Moreover, the combination of MPH with DES produced the most dramatic beneficial effects. Serum levels of interleukin-1β (IL-1β) and IL-6 were elevated in the PTSD-like group compared with the control group, and were decreased by MPH, FLU, DES or the combination drug treatments, with the combination of DES+MPH producing the most complete rescue of the inflammatory response. Considering the versatile symptoms of PTSD, our results suggest a new combined treatment for PTSD comprising the antidepressant DES and the psychostimulant MPH.

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Section: Discussionsupporting

confidence: 51%

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model

et al. 2014

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“…We wondered whether depressive-like behaviour might be dependent on nociceptive changes elicited by CFA in mice. There is a series of previous publications demonstrating that antidepressant drugs can display analgesic effects in different inflammation models, and some of them also show anti-inflammatory effects [21,48,49]. However, in the present study, we decided to evaluate dipyrone – considering its inability to interfere with inflammation; we also evaluated pregabalin – that represents a modern pharmacological alternative for treating chronic pain, even in mood-related situations, such as fibromyalgia [50].…”

Section: Discussionmentioning

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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“…Fluoxetine (50 mg/kg) was administered by gavage to experimental animals as an oral solution (Prozac™ 20 mg/5 ml, oral solution bottle of fluoxetine hydrochloride, Lilly Laboratories, France) 18 h before hyperbaric exposure, while the wild type control group (WT cont ) received a similar saccharine fluoxetine-free solution (7.4 g/kg). This high dose of fluoxetine was determined on the basis of previous results from a mouse model of ischemia (Jin et al, 2009 ; Blatteau et al, 2012 ; Taguchi et al, 2012 ).…”

Section: Methodsmentioning

confidence: 99%

“…When used in a single high dose, fluoxetine is also believed to mediate neuroprotection (Pariente et al, 2001 ; Chollet et al, 2011 ; Taguchi et al, 2012 ) by inhibiting NMDA-R (Vizi et al, 2013 ), regulating inflammatory effects (Kubera et al, 2001 ; Jin et al, 2009 ; Lim et al, 2009 ) and algesia (Kostadinov et al, 2014 ). We have previously demonstrated that WT mice treated with fluoxetine are more resistant to DCS and that fluoxetine inhibits the inflammatory process by reducing the level of circulating IL-6, a pro-inflammatory cytokine (Blatteau et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

et al. 2016

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In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate.

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Protective Effects of Fluoxetine on Decompression Sickness in Mice

Cited by 21 publications

References 31 publications

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model

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

Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

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